Is ABCA4 p.Asp1995Val (c.5984A>T) pathogenic?

ABCA4 p.Asp1995Val (c.5984A>T) is classified Conflicting classifications of pathogenicity in ABCA4 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-06-17). AlphaMissense: ambiguous (0.3449); Ultra-rare (popmax 0.0748%, afr).

How common is ABCA4 p.Asp1995Val (c.5984A>T) in the general population?

ABCA4 p.Asp1995Val (c.5984A>T) is ultra-rare (popmax 0.0748%, afr) (gnomAD).

What do computational predictors say about ABCA4 p.Asp1995Val (c.5984A>T)?

AlphaMissense predicts ambiguous (score 0.3449) — an in-silico prediction, not a clinical call.

ABCA4 p.Asp1995Val

c.5984A>T · rs141489669 · VCV1058512

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3449 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0748%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3449	ambiguous
REVEL	0.787	moderately pathogenic-leaning
SaProt	LLR -12.12	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	25.3	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 0.0748% African / African-American · 56/74,910 alleles

Filtering AF 0.059% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0534%

Overall 0.00372% 60/1,613,898 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0748%	1,338
Remaining individualsnot grpmax-eligible	0.0048%	20,827
Admixed American	0.00167%	59,994

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.Asp1995Val
Coding: c.5984A>T
MANE Select: NM_000350
dbSNP: rs141489669
Type: single nucleotide variant
Location: chr1:94007655 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 1995: 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 2 domain; 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 β-strand

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

Similar variants

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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
ABCA4 c.4773+3A>G Pathogenic ★★★ same type
ABCA4 c.5018+2T>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-asp1995val (accessed [today's date]).

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