Is ABCA7 p.Leu795= (c.2385G>A) pathogenic?

ABCA7 p.Leu795= (c.2385G>A) is classified Benign in ABCA7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-02-23). Common (popmax 41.7%, eas) — too common for a highly-penetrant pathogenic allele.

ABCA7 p.Leu795=

Q: How common is ABCA7 p.Leu795= (c.2385G>A) in the general population?

ABCA7 p.Leu795= (c.2385G>A) is common (popmax 41.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2385G>A · rs4147914 · VCV1257803

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 41.7%, eas) — 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 0.96	GERP -2.7, phastCons 1
Overall
CADD	5.607	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 41.7% East Asian · 18,642/44,672 alleles

Filtering AF 41.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 41%

Overall 15.7% 250,944/1,602,504 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	41.7%	2
South Asian	26.5%	4
Amishnot grpmax-eligible	23.6%	4
Ashkenazi Jewishnot grpmax-eligible	21.9%	5
Remaining individualsnot grpmax-eligible	17.6%	6
Middle Eastern	17.2%	6
African / African-American	16.5%	6
European (non-Finnish)	13.9%	7
Finnishnot grpmax-eligible	13.1%	8
Admixed American	11.5%	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.Leu795=
Coding: c.2385G>A
MANE Select: NM_019112
dbSNP: rs4147914
Type: single nucleotide variant
Location: chr19:1049270 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.77 · 6 PDB

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-leu795 (accessed [today's date]).

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