Is ABCA4 p.Tyr954= (c.2862C>T) pathogenic?

ABCA4 p.Tyr954= (c.2862C>T) is classified Likely benign in ABCA4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-02-22). Ultra-rare (popmax 0.0802%, eas); Associated with inherited retinal dystrophy.

What condition is associated with ABCA4 p.Tyr954= (c.2862C>T)?

ABCA4 p.Tyr954= (c.2862C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is ABCA4 p.Tyr954= (c.2862C>T) in the general population?

ABCA4 p.Tyr954= (c.2862C>T) is ultra-rare (popmax 0.0802%, eas) (gnomAD).

ABCA4 p.Tyr954=

c.2862C>T · rs757870374 · VCV1116367

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0802%, eas)

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -5
Overall
CADD	0.189	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0802% East Asian · 36/44,886 alleles

Filtering AF 0.0595% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0524%

Overall 0.00359% 58/1,614,014 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0802%	1,247
South Asian	0.00659%	15,181
African / African-American	0.00401%	24,968
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Admixed American	0.00333%	30,000
European (non-Finnish)	0.000847%	118,002

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.Tyr954=
Coding: c.2862C>T
MANE Select: NM_000350
dbSNP: rs757870374
Type: single nucleotide variant
Location: chr1:94046975 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 954: 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 disulfide bond

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCA4 p.Tyr954Ser Pathogenic/Likely pathogenic ★★ same residue
ABCA4 p.Tyr954Ter Pathogenic ★ same residue
ABCA4 c.1937+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-tyr954 (accessed [today's date]).

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