Is ABCA4 p.Ile1802Val (c.5404A>G) pathogenic?

ABCA4 p.Ile1802Val (c.5404A>G) is classified Uncertain significance in ABCA4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-26). AlphaMissense: likely benign (0.0843); Very rare (popmax 0.00934%, afr).

How common is ABCA4 p.Ile1802Val (c.5404A>G) in the general population?

ABCA4 p.Ile1802Val (c.5404A>G) is very rare (popmax 0.00934%, afr) (gnomAD).

What do computational predictors say about ABCA4 p.Ile1802Val (c.5404A>G)?

AlphaMissense predicts likely benign (score 0.0843) — an in-silico prediction, not a clinical call.

ABCA4 p.Ile1802Val

c.5404A>G · rs974596881 · VCV1052497

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0843 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0843	likely benign
REVEL	0.421	indeterminate
SaProt	LLR -8.64	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 1.5	GERP 0.67, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	18.61	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00934% African / African-American · 7/74,910 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000929% 15/1,614,054 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00934%	10,701
Remaining individualsnot grpmax-eligible	0.008%	12,498
Admixed American	0.00167%	60,006
European (non-Finnish)	0.000169%	590,016

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.Ile1802Val
Coding: c.5404A>G
MANE Select: NM_000350
dbSNP: rs974596881
Type: single nucleotide variant
Location: chr1:94014599 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 1802: 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); an α-helix

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

Similar variants

ABCA4 p.Ile1802= Uncertain significance ★★★ same residue
ABCA4 p.Ile1802Thr Uncertain significance ★ ⚠ same residue
ABCA4 c.1937+1G>A Pathogenic ★★★ same type
ABCA4 c.3328+2T>A Pathogenic ★★★ same type
ABCA4 c.3523-1G>A Pathogenic ★★★ same type
ABCA4 c.4253+43G>A Pathogenic ★★★ same type
ABCA4 c.4254-1G>C Pathogenic ★★★ same type
ABCA4 c.4352+1G>A Pathogenic ★★★ same type

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-ile1802val (accessed [today's date]).

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