Is ABCA7 p.Leu1139= (c.3417C>G) pathogenic?

ABCA7 p.Leu1139= (c.3417C>G) is classified Benign in ABCA7 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-05). Common (popmax 25.2%, sas) — too common for a highly-penetrant pathogenic allele; Associated with ABCA7-related disorder.

What condition is associated with ABCA7 p.Leu1139= (c.3417C>G)?

ABCA7 p.Leu1139= (c.3417C>G) is associated with ABCA7-related disorder (ClinVar).

ABCA7 p.Leu1139=

Q: How common is ABCA7 p.Leu1139= (c.3417C>G) in the general population?

ABCA7 p.Leu1139= (c.3417C>G) is common (popmax 25.2%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3417C>G · rs3752241 · VCV3060111

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 25.2%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

ABCA7-related disorder

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 -5.6	GERP -3.7
Overall
CADD	0.723	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 25.2% South Asian · 21,729/86,170 alleles

Filtering AF 24.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 24.8%

Overall 17.1% 267,523/1,561,844 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	25.2%	4
African / African-American	18.7%	5
East Asian	18.4%	5
Remaining individualsnot grpmax-eligible	17.9%	6
Ashkenazi Jewishnot grpmax-eligible	17.2%	6
European (non-Finnish)	16.8%	6
Middle Eastern	16.7%	6
Finnishnot grpmax-eligible	16.4%	6
Amishnot grpmax-eligible	12.8%	8
Admixed American	8.85%	11

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.Leu1139=
Coding: c.3417C>G
MANE Select: NM_019112
dbSNP: rs3752241
Type: single nucleotide variant
Location: chr19:1053525 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.77 · 6 PDB
Residue 1139: an α-helix

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

Disease context

ABCA7-related disorder

Similar variants

ABCA7 c.4417-1G>C Likely pathogenic ★ same condition
ABCA7 p.Gln1083Ter Pathogenic ★ same condition
ABCA7 p.Arg1754Ter Likely pathogenic same condition
ABCA7 p.Glu269Ter Likely pathogenic same condition
ABCA7 c.790+10T>G Benign same condition
ABCA7 c.-9A>G Benign same condition
ABCA7 p.Ala1441= Likely benign same condition
ABCA7 p.Ala1864= Benign same condition

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-leu1139 (accessed [today's date]).

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