Is ABCA7 p.Ala589Val (c.1766C>T) pathogenic?

ABCA7 p.Ala589Val (c.1766C>T) is classified Likely benign in ABCA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). AlphaMissense: likely benign (0.099); Rare (popmax 0.553%, afr).

How common is ABCA7 p.Ala589Val (c.1766C>T) in the general population?

ABCA7 p.Ala589Val (c.1766C>T) is rare (popmax 0.553%, afr) (gnomAD).

What do computational predictors say about ABCA7 p.Ala589Val (c.1766C>T)?

AlphaMissense predicts likely benign (score 0.099) — an in-silico prediction, not a clinical call.

ABCA7 p.Ala589Val

c.1766C>T · rs144979723 · VCV735385

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.099 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.553%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.099	likely benign
REVEL	0.3	indeterminate
SaProt	LLR -8.19	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.7	GERP -3.1
Regional constraint	o/e 1.14	unconstrained · MANE · 24 kb · p 5.6e-14 · regional, not allelic
Overall
CADD	19.23	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 0.553% African / African-American · 367/66,350 alleles

Filtering AF 0.507% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.488%

Overall 0.0298% 468/1,568,612 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.553%	181
Admixed American	0.0672%	1,487
Remaining individualsnot grpmax-eligible	0.0558%	1,793
South Asian	0.00461%	21,669
East Asian	0.0023%	43,392
European (non-Finnish)	0.00223%	44,830

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: ABCA7
Protein: p.Ala589Val
Coding: c.1766C>T
MANE Select: NM_019112
dbSNP: rs144979723
Type: single nucleotide variant
Location: chr19:1046945 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.77 · 6 PDB
Residue 589: an α-helix

Full ABCA7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA7 p.Ala589= Likely benign same residue
ABCA7 c.2684+5G>A Uncertain significance ★★ same type
ABCA7 c.3578-2A>G Uncertain significance ★★ same type
ABCA7 p.Arg1026Cys Uncertain significance ★★ ⚠ same type
ABCA7 p.Arg652Cys Uncertain significance ★★ ⚠ same type
ABCA7 p.Arg880Trp Uncertain significance ★★ ⚠ same type
ABCA7 p.Asp1452Asn Uncertain significance ★★ ⚠ same type
ABCA7 p.Asp2085Asn Uncertain significance ★★ ⚠ 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/abca7-p-ala589val (accessed [today's date]).

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