Is ABCA4 p.Ala389= (c.1167G>A) pathogenic?

ABCA4 p.Ala389= (c.1167G>A) is classified Likely benign in ABCA4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-02-29). Ultra-rare (popmax 0.0143%, sas).

How common is ABCA4 p.Ala389= (c.1167G>A) in the general population?

ABCA4 p.Ala389= (c.1167G>A) is ultra-rare (popmax 0.0143%, sas) (gnomAD).

ABCA4 p.Ala389=

c.1167G>A · rs372704965 · VCV1581715

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, sas)

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 -1.6	GERP -3.9
Overall
CADD	4.948	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0143% South Asian · 13/91,080 alleles

Filtering AF 0.00844% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00661%

Overall 0.00192% 31/1,614,056 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0143%	7,006
Remaining individualsnot grpmax-eligible	0.0032%	31,243
East Asian	0.00223%	44,894
European (non-Finnish)	0.00127%	78,670

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.Ala389=
Coding: c.1167G>A
MANE Select: NM_000350
dbSNP: rs372704965
Type: single nucleotide variant
Location: chr1:94079394 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 389: 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); an α-helix; a disulfide bond

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

Similar variants

ABCA4 p.Ala389Val Uncertain significance ★ ⚠ same residue
ABCA4 c.1937+1G>A Pathogenic ★★★ same type
ABCA4 c.3328+2T>A Pathogenic ★★★ same type
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

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-ala389 (accessed [today's date]).

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