Is ABCA4 p.Arg1098Cys (c.3292C>T) pathogenic?

ABCA4 p.Arg1098Cys (c.3292C>T) is classified Pathogenic/Likely pathogenic in ABCA4 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-06-07). AlphaMissense: likely pathogenic (0.5865); Ultra-rare (popmax 0.0329%, mid); Associated with inherited retinal dystrophy.

What condition is associated with ABCA4 p.Arg1098Cys (c.3292C>T)?

ABCA4 p.Arg1098Cys (c.3292C>T) is associated with inherited retinal dystrophy, age related macular degeneration 2, severe early-childhood-onset retinal dystrophy (ClinVar).

How common is ABCA4 p.Arg1098Cys (c.3292C>T) in the general population?

ABCA4 p.Arg1098Cys (c.3292C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about ABCA4 p.Arg1098Cys (c.3292C>T)?

AlphaMissense predicts likely pathogenic (score 0.5865) — an in-silico prediction, not a clinical call.

ABCA4 p.Arg1098Cys

c.3292C>T · rs756840095 · VCV236100

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely pathogenic

0.5865 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.5865	likely pathogenic ✓ concordant with ClinVar
REVEL	0.894	moderately pathogenic-leaning
SaProt	LLR -12.57	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.00285% 46/1,614,088 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
Admixed American	0.0217%	4,616
South Asian	0.00549%	18,218
Remaining individualsnot grpmax-eligible	0.0032%	31,244
East Asian	0.00223%	44,886
European (non-Finnish)	0.00195%	51,307

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.Arg1098Cys
Coding: c.3292C>T
MANE Select: NM_000350
dbSNP: rs756840095
Type: single nucleotide variant
Location: chr1:94042797 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 1098: 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 1 domain; an α-helix; a disulfide bond

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: age related macular degeneration 2 severe early-childhood-onset retinal dystrophy retinitis pigmentosa 19 cone-rod dystrophy 3

Similar variants

ABCA4 p.Arg1098= Likely benign ★★ same residue
ABCA4 p.Arg1098His Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCA4 c.1937+1G>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-arg1098cys (accessed [today's date]).

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