Is ABCA7 p.Val915= (c.2745A>G) pathogenic?

ABCA7 p.Val915= (c.2745A>G) is classified Benign in ABCA7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2020-09-21). Common (popmax 41.5%, mid) — too common for a highly-penetrant pathogenic allele.

ABCA7 p.Val915=

Q: How common is ABCA7 p.Val915= (c.2745A>G) in the general population?

ABCA7 p.Val915= (c.2745A>G) is common (popmax 41.5%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2745A>G · rs3752240 · VCV1241058

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 41.5%, mid) — too common for a highly-penetrant pathogenic allele

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 -20	GERP -2.7
Overall
CADD	0.015	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 41.5% Middle Eastern · 2,511/6,044 alleles

Filtering AF 40.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 39.6%

Overall 34.4% 554,652/1,610,496 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	41.5%	2
Ashkenazi Jewishnot grpmax-eligible	40.2%	2
Admixed American	38.7%	3
African / African-American	36.6%	3
European (non-Finnish)	35.5%	3
Finnishnot grpmax-eligible	35.4%	3
Remaining individualsnot grpmax-eligible	33.2%	3
Amishnot grpmax-eligible	30.1%	3
South Asian	26.1%	4
East Asian	10.8%	9

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.Val915=
Coding: c.2745A>G
MANE Select: NM_019112
dbSNP: rs3752240
Type: single nucleotide variant
Location: chr19:1051215 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.77 · 6 PDB
Residue 915: a turn; the abc transporter 1 domain

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-val915 (accessed [today's date]).

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