Is ABCA4 p.Asp1102Tyr (c.3304G>T) pathogenic?

ABCA4 p.Asp1102Tyr (c.3304G>T) is classified Pathogenic/Likely pathogenic in ABCA4 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-11-27). AlphaMissense: likely pathogenic (0.7141); Very rare (popmax 0.00668%, eas); Associated with ABCA4-related disorder.

What condition is associated with ABCA4 p.Asp1102Tyr (c.3304G>T)?

ABCA4 p.Asp1102Tyr (c.3304G>T) is associated with ABCA4-related disorder, age related macular degeneration 2, severe early-childhood-onset retinal dystrophy (ClinVar).

How common is ABCA4 p.Asp1102Tyr (c.3304G>T) in the general population?

ABCA4 p.Asp1102Tyr (c.3304G>T) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about ABCA4 p.Asp1102Tyr (c.3304G>T)?

AlphaMissense predicts likely pathogenic (score 0.7141) — an in-silico prediction, not a clinical call.

ABCA4 p.Asp1102Tyr

c.3304G>T · rs138641544 · VCV1456034

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.7141 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABCA4-related disorder

Computational evidence

Protein change
AlphaMissense	0.7141	likely pathogenic ✓ concordant with ClinVar
REVEL	0.973	strongly pathogenic-leaning
SaProt	LLR -11.29	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 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	28.6	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 0.00668% East Asian · 3/44,886 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000186% 3/1,614,076 alleles · very rare

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.Asp1102Tyr
Coding: c.3304G>T
MANE Select: NM_000350
dbSNP: rs138641544
Type: single nucleotide variant
Location: chr1:94042785 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 1102: 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; a UniProt-annotated variant site (in); an α-helix; a disulfide bond

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

Disease context

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

Similar variants

ABCA4 p.Asp1102Val Pathogenic ★ same residue
ABCA4 p.Asp1102Ala Uncertain significance ★ ⚠ same residue
ABCA4 p.Asp1102Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCA4 p.Asp1102Gly 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

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-asp1102tyr (accessed [today's date]).

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