Is ABCA4 p.Arg511His (c.1532G>A) pathogenic?

ABCA4 p.Arg511His (c.1532G>A) is classified Conflicting classifications of pathogenicity in ABCA4 (ClinVar, Conflicting submitters, 11 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.062); Rare (popmax 0.459%, sas); Associated with ABCA4-related disorder.

What condition is associated with ABCA4 p.Arg511His (c.1532G>A)?

ABCA4 p.Arg511His (c.1532G>A) is associated with ABCA4-related disorder, severe early-childhood-onset retinal dystrophy, inherited retinal dystrophy (ClinVar).

How common is ABCA4 p.Arg511His (c.1532G>A) in the general population?

ABCA4 p.Arg511His (c.1532G>A) is rare (popmax 0.459%, sas) (gnomAD).

What do computational predictors say about ABCA4 p.Arg511His (c.1532G>A)?

AlphaMissense predicts likely benign (score 0.062) — an in-silico prediction, not a clinical call.

ABCA4 p.Arg511His

c.1532G>A · rs140482171 · VCV283387

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.062 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.459%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ABCA4-related disorder

Computational evidence

Protein change
AlphaMissense	0.062	likely benign
REVEL	0.336	indeterminate
SaProt	LLR -6.71	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.56	GERP -1.3, phastCons 0.007
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	16.27	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 0.459% South Asian · 417/90,922 alleles

Filtering AF 0.422% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.408%

Overall 0.0801% 1,293/1,613,274 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.459%	218
Middle Eastern	0.116%	864
Remaining individualsnot grpmax-eligible	0.072%	1,388
European (non-Finnish)	0.0675%	1,482
Admixed American	0.0167%	5,999
African / African-American	0.016%	6,252
East Asian	0.0134%	7,476

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.Arg511His
Coding: c.1532G>A
MANE Select: NM_000350
dbSNP: rs140482171
Type: single nucleotide variant
Location: chr1:94077712 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 511: 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); an α-helix; a disulfide bond

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

Disease context

Also linked: severe early-childhood-onset retinal dystrophy inherited retinal dystrophy Stargardt disease

Similar variants

ABCA4 p.Arg511Cys Pathogenic ★★★ ⚠ 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
ABCA4 c.5018+2T>A 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-arg511his (accessed [today's date]).

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