Is ARMC5 p.Arg764Gln (c.2291G>A) pathogenic?

ARMC5 p.Arg764Gln (c.2291G>A) is classified Uncertain significance in ARMC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: likely benign (0.3388); Very rare (popmax 0.0022%, sas).

How common is ARMC5 p.Arg764Gln (c.2291G>A) in the general population?

ARMC5 p.Arg764Gln (c.2291G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about ARMC5 p.Arg764Gln (c.2291G>A)?

AlphaMissense predicts likely benign (score 0.3388) — an in-silico prediction, not a clinical call.

ARMC5 p.Arg764Gln

c.2291G>A · VCV4281136

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3388 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3388	likely benign
REVEL	0.462	indeterminate
SaProt	LLR -12.94	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 4,961 bp · p 1.6e-10 · regional, not allelic
Overall
CADD	26.0	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 0.0022% South Asian · 2/91,070 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000411% 6/1,460,600 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,535
European (non-Finnish)	0.000339%	294,961

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: ARMC5
Protein: p.Arg764Gln
Coding: c.2291G>A
MANE Select: NM_001105247
Type: single nucleotide variant
Location: chr16:31466372 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.27
Residue 764: a UniProt-annotated variant site (in aimah2; uncertain significance); a UniProt-annotated variant site (in aimah2); the btb domain

Full ARMC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARMC5 p.Arg764Ter Pathogenic ★ same residue
ARMC5 p.Arg173Ter Pathogenic ★★ same type
ARMC5 p.Ala55Val Uncertain significance ★★ ⚠ same type
ARMC5 p.Arg611Leu Uncertain significance ★★ ⚠ same type
ARMC5 p.Arg690Gln Uncertain significance ★★ ⚠ same type
ARMC5 p.Pro606Leu Uncertain significance ★★ ⚠ same type
ARMC5 p.Ser266Thr Uncertain significance ★★ ⚠ same type
ARMC5 p.Trp801Cys 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/armc5-p-arg764gln (accessed [today's date]).

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