Is ABCA4 p.Cys1502= (c.4506C>T) pathogenic?

ABCA4 p.Cys1502= (c.4506C>T) is classified Conflicting classifications of pathogenicity in ABCA4 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-09-02). Very rare (popmax 0.00112%, nfe); Associated with inherited retinal dystrophy.

What condition is associated with ABCA4 p.Cys1502= (c.4506C>T)?

ABCA4 p.Cys1502= (c.4506C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is ABCA4 p.Cys1502= (c.4506C>T) in the general population?

ABCA4 p.Cys1502= (c.4506C>T) is very rare (popmax 0.00112%, nfe) (gnomAD).

ABCA4 p.Cys1502=

c.4506C>T · rs61750149 · VCV99290

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00112%, nfe)

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 5.1	GERP -0.004, phastCons 1
Overall
CADD	6.736	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00112% European (non-Finnish) · 13/1,159,316 alleles

Filtering AF 0.000626% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000482%

Overall 0.000888% 14/1,576,208 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00164%	61,010
European (non-Finnish)grpmax	0.00112%	89,178

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Cys1502=
Coding: c.4506C>T
MANE Select: NM_000350
dbSNP: rs61750149
Type: single nucleotide variant
Location: chr1:94029478 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 1502: 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 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.Cys1502Phe Pathogenic/Likely pathogenic ★★ same residue
ABCA4 p.Cys1502Ter 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-cys1502 (accessed [today's date]).

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