Is ABCA7 p.Arg165= (c.495C>T) pathogenic?

ABCA7 p.Arg165= (c.495C>T) is classified Likely benign in ABCA7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-24). Rare (popmax 0.171%, afr).

How common is ABCA7 p.Arg165= (c.495C>T) in the general population?

ABCA7 p.Arg165= (c.495C>T) is rare (popmax 0.171%, afr) (gnomAD).

ABCA7 p.Arg165=

c.495C>T · rs140835505 · VCV727265

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.171%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.36	donor gain · deltas
Constraint at this position
Conservation	phyloP -0.029	GERP -2
Overall
CADD	2.646	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.171% African / African-American · 128/75,026 alleles

Filtering AF 0.147% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.137%

Overall 0.0132% 213/1,610,152 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.171%	586
Middle Eastern	0.0661%	1,514
Remaining individualsnot grpmax-eligible	0.0321%	3,118
South Asian	0.022%	4,545
Admixed American	0.00834%	11,986
European (non-Finnish)	0.00306%	32,716

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.Arg165=
Coding: c.495C>T
MANE Select: NM_019112
dbSNP: rs140835505
Type: single nucleotide variant
Location: chr19:1042394 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.77 · 6 PDB
Residue 165: a disulfide bond

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-arg165 (accessed [today's date]).

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