Is ABCA4 p.Arg1556fs (c.4666del) pathogenic?

ABCA4 p.Arg1556fs (c.4666del) is classified Pathogenic/Likely pathogenic in ABCA4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-27). Absent from gnomAD; Associated with ABCA4-related disorder.

What condition is associated with ABCA4 p.Arg1556fs (c.4666del)?

ABCA4 p.Arg1556fs (c.4666del) is associated with ABCA4-related disorder (ClinVar).

How common is ABCA4 p.Arg1556fs (c.4666del) in the general population?

ABCA4 p.Arg1556fs (c.4666del) is absent from gnomAD (gnomAD).

ABCA4 p.Arg1556fs

c.4666del · rs2101025946 · VCV1073491

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

ABCA4-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 32 of 50
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 2, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ABCA4
Protein: p.Arg1556fs
Coding: c.4666del
MANE Select: NM_000350
dbSNP: rs2101025946
Type: Deletion
Location: chr1:94023387 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 1556: 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); a UniProt-annotated variant site (in stgd1 and cord3; uncertain significance)

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

Disease context

ABCA4-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCA4 p.Arg1556Thr Pathogenic ★★ same residue
ABCA4 c.4634+1del Pathogenic ★★ same condition
ABCA4 c.5899-2del Pathogenic ★★ same condition
ABCA4 c.6729+5_6729+19del Pathogenic/Likely pathogenic ★★ same condition
ABCA4 p.Ala1324fs Pathogenic ★★ same condition
ABCA4 p.Ala222fs Pathogenic ★★ same condition
ABCA4 p.Arg1705_Val1706insTer Pathogenic/Likely pathogenic ★★ same condition
ABCA4 p.Arg1843_Gly1844del Pathogenic/Likely 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-arg1556fs (accessed [today's date]).

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