Is ABCA4 p.Ala1021= (c.3063T>G) pathogenic?

ABCA4 p.Ala1021= (c.3063T>G) is classified Conflicting classifications of pathogenicity in ABCA4 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-03-14). Ultra-rare (popmax 0.0156%, eas); Associated with ABCA4-related disorder.

What condition is associated with ABCA4 p.Ala1021= (c.3063T>G)?

ABCA4 p.Ala1021= (c.3063T>G) is associated with ABCA4-related disorder (ClinVar).

How common is ABCA4 p.Ala1021= (c.3063T>G) in the general population?

ABCA4 p.Ala1021= (c.3063T>G) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

ABCA4 p.Ala1021=

c.3063T>G · rs886046565 · VCV298253

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Conditions

ABCA4-related disorder

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 -4.4	GERP -5.4
Overall
CADD	0.892	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,868 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.000479% 7/1,461,886 alleles · ultra-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.Ala1021=
Coding: c.3063T>G
MANE Select: NM_000350
dbSNP: rs886046565
Type: single nucleotide variant
Location: chr1:94043463 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 1021: 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; an α-helix; a disulfide bond

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

Disease context

ABCA4-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCA4 c.1099+2T>G Pathogenic/Likely pathogenic ★★ same condition
ABCA4 c.160+5G>C Pathogenic/Likely pathogenic ★★ same condition
ABCA4 c.1937+1G>C Pathogenic/Likely pathogenic ★★ same condition
ABCA4 c.1938-619A>G Pathogenic/Likely pathogenic ★★ same condition
ABCA4 c.2160+1G>C Pathogenic ★★ same condition
ABCA4 c.2161-8G>A Pathogenic ★★ same condition
ABCA4 c.2382+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCA4 c.2383-1G>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-ala1021 (accessed [today's date]).

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