Is ABCA4 p.Arg2263Gln (c.6788G>A) pathogenic?

ABCA4 p.Arg2263Gln (c.6788G>A) is classified Conflicting classifications of pathogenicity in ABCA4 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-02-25). AlphaMissense: likely benign (0.134); Very rare (popmax 0.00446%, eas); Associated with ABCA4-related retinopathy.

What condition is associated with ABCA4 p.Arg2263Gln (c.6788G>A)?

ABCA4 p.Arg2263Gln (c.6788G>A) is associated with ABCA4-related retinopathy (ClinVar).

How common is ABCA4 p.Arg2263Gln (c.6788G>A) in the general population?

ABCA4 p.Arg2263Gln (c.6788G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about ABCA4 p.Arg2263Gln (c.6788G>A)?

AlphaMissense predicts likely benign (score 0.134) — an in-silico prediction, not a clinical call.

ABCA4 p.Arg2263Gln

c.6788G>A · rs281865407 · VCV1015873

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.134 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

ABCA4-related retinopathy

Computational evidence

Protein change
AlphaMissense	0.134	likely benign
REVEL	0.393	indeterminate
SaProt	LLR -5.67	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	24.0	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 0.00446% East Asian · 2/44,874 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000682% 11/1,613,986 alleles · very rare exomes 11/1,461,696 · genomes 0/152,290 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,437
Admixed American	0.00333%	30,013
South Asian	0.00329%	30,360
African / African-American	0.00133%	75,036
European (non-Finnish)	0.000254%	393,342

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.Arg2263Gln
Coding: c.6788G>A
MANE Select: NM_000350
dbSNP: rs281865407
Type: single nucleotide variant
Location: chr1:93996137 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 2263: 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); 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; uncertain significance; also found in a patient with chorioretinal atrophy; uncertain significance); a UniProt-annotated variant site (in stgd1)

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

Disease context

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

Similar variants

ABCA4 p.Arg2263Gly Likely pathogenic ★ ⚠ same residue
ABCA4 p.Arg2263Ter Likely 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

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-arg2263gln (accessed [today's date]).

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