Is ABCA4 p.Arg2030Ter (c.6088C>T) pathogenic?

ABCA4 p.Arg2030Ter (c.6088C>T) is classified Pathogenic/Likely pathogenic in ABCA4 (ClinVar, Multiple submitters, 29 submitters; last evaluated 2026-06-12). Ultra-rare (popmax 0.0165%, mid); Associated with Autosomal recessive ABCA4-related disorders.

What condition is associated with ABCA4 p.Arg2030Ter (c.6088C>T)?

ABCA4 p.Arg2030Ter (c.6088C>T) is associated with Autosomal recessive ABCA4-related disorders, retinal disorder, age related macular degeneration 2 (ClinVar).

How common is ABCA4 p.Arg2030Ter (c.6088C>T) in the general population?

ABCA4 p.Arg2030Ter (c.6088C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

ABCA4 p.Arg2030Ter

c.6088C>T · rs61751383 · VCV7907

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 29 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Autosomal recessive ABCA4-related disorders

ClinGen expert panel — ABCA4 VCEP

Pathogenic for ABCA4-related retinopathy. Applied ACMG criteria (verbatim):

PVS1 PM2_Supporting PS4

Curation rationale (ClinGen, verbatim)

NM_000350.3(ABCA4):c.6088C>T; p.Arg2030Ter variant in ABCA4 is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 44 of 50 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). The total minor allele frequency in gnomAD v4.1.1 is 0.00001425, which is lower than the threshold (<0.0001) for PM2_Supporting. The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls with an OR of 195.4 and CI of 62.90 to 953.37, which is above the ABCA4 VCEP threshold of ≥5 where the CI does not contain 1 (PS4; PMID: 35120629). In summary, this variant meets the criteria to be classified as pathogenic for ABCA4-related retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen ABCA4 VCEP (Specification Version 1.0), as specified by the ClinGen ABCA4 Variant Curation Expert Panel: PVS1, PS4, PM2_Supporting.

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 44 of 50
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -1.6, phastCons 0.77
Overall
CADD	46.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00844% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00661%

Overall 0.00142% 23/1,614,096 alleles · ultra-rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.11%	912
Middle Easterngrpmax	0.0165%	6,062
South Asian	0.0143%	7,006
Remaining individualsnot grpmax-eligible	0.0032%	31,253
Admixed American	0.00167%	60,016
European (non-Finnish)	0.000424%	236,002

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ABCA4
Protein: p.Arg2030Ter
Coding: c.6088C>T
MANE Select: NM_000350
dbSNP: rs61751383
Type: single nucleotide variant
Location: chr1:94005500 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 2030: a UniProt-annotated variant site (in cord3; uncertain significance); a UniProt-annotated variant site (in stgd1; uncertain significance); a UniProt-annotated variant site (found in a patient with chorioretinal atrophy; uncertain significance); a UniProt-annotated variant site (found in a patient with macular dystrophy; uncertain significance); the abc transporter 2 domain; a UniProt-annotated variant site (in stgd1 and cord3; uncertain significance); a UniProt-annotated variant site (sequence variant); a UniProt-annotated variant site (in stgd1 and ffm; uncertain significance); a UniProt-annotated variant site (in stgd1 and ffm)

Full ABCA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Autosomal recessive ABCA4-related disorders

Also linked: retinal disorder age related macular degeneration 2 severe early-childhood-onset retinal dystrophy retinitis pigmentosa 19 cone-rod dystrophy 3 Leber congenital amaurosis 14 inherited retinal dystrophy Stargardt disease ABCA4-related retinopathy

Similar variants

ABCA4 p.Arg2030Gln Pathogenic ★★★ ⚠ same residue
ABCA4 c.1937+1G>A Pathogenic ★★★ same condition
ABCA4 c.3328+2T>A Pathogenic ★★★ same condition
ABCA4 c.3523-1G>A Pathogenic ★★★ same condition
ABCA4 c.4253+43G>A Pathogenic ★★★ same condition
ABCA4 c.4254-1G>C Pathogenic ★★★ same condition
ABCA4 c.4352+1G>A Pathogenic ★★★ same condition
ABCA4 c.4773+3A>G Pathogenic ★★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/abca4-p-arg2030ter (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown