Is ABCA7 p.Val1244Met (c.3730G>A) pathogenic?

ABCA7 p.Val1244Met (c.3730G>A) is classified Likely benign in ABCA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1475); Rare (popmax 0.232%, afr).

How common is ABCA7 p.Val1244Met (c.3730G>A) in the general population?

ABCA7 p.Val1244Met (c.3730G>A) is rare (popmax 0.232%, afr) (gnomAD).

What do computational predictors say about ABCA7 p.Val1244Met (c.3730G>A)?

AlphaMissense predicts likely benign (score 0.1475) — an in-silico prediction, not a clinical call.

ABCA7 p.Val1244Met

c.3730G>A · rs138363826 · VCV760554

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1475 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.232%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1475	likely benign
REVEL	0.472	indeterminate
SaProt	LLR -9.14	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 1.6	GERP -3.4, phastCons 0.55
Regional constraint	o/e 1.14	unconstrained · MANE · 24 kb · p 5.6e-14 · regional, not allelic
Overall
CADD	21.0	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 0.232% African / African-American · 174/74,978 alleles

Filtering AF 0.204% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.193%

Overall 0.0132% 212/1,609,432 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.232%	431
Middle Eastern	0.0378%	2,649
Admixed American	0.0167%	5,999
Remaining individualsnot grpmax-eligible	0.0129%	7,779
European (non-Finnish)	0.00144%	69,284
South Asian	0.0011%	91,004

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.Val1244Met
Coding: c.3730G>A
MANE Select: NM_019112
dbSNP: rs138363826
Type: single nucleotide variant
Location: chr19:1054573 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.77 · 6 PDB
Residue 1244: an α-helix

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

Similar variants

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
ABCA7 p.Gln925Ter 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-val1244met (accessed [today's date]).

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