Is ABCA7 p.Ala1493Ser (c.4477G>T) pathogenic?

ABCA7 p.Ala1493Ser (c.4477G>T) is classified Uncertain significance in ABCA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-03). AlphaMissense: likely benign (0.2172); Very rare (popmax 0.00439%, sas).

How common is ABCA7 p.Ala1493Ser (c.4477G>T) in the general population?

ABCA7 p.Ala1493Ser (c.4477G>T) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about ABCA7 p.Ala1493Ser (c.4477G>T)?

AlphaMissense predicts likely benign (score 0.2172) — an in-silico prediction, not a clinical call.

ABCA7 p.Ala1493Ser

c.4477G>T · VCV3856959

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2172 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2172	likely benign
REVEL	0.581	indeterminate
SaProt	LLR -8.93	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.36	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 24 kb · p 5.6e-14 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,072 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000479% 7/1,461,260 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,768
Remaining individualsnot grpmax-eligible	0.0032%	31,249
European (non-Finnish)	8.47e-05%	1,179,962

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.Ala1493Ser
Coding: c.4477G>T
MANE Select: NM_019112
Type: single nucleotide variant
Location: chr19:1056390 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.77 · 6 PDB
Residue 1493: an α-helix

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

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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-ala1493ser (accessed [today's date]).

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