Is ARMC2 p.Ala655Val (c.1964C>T) pathogenic?

ARMC2 p.Ala655Val (c.1964C>T) is classified Uncertain significance in ARMC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-27). AlphaMissense: likely benign (0.1662); Rare (popmax 0.101%, mid).

How common is ARMC2 p.Ala655Val (c.1964C>T) in the general population?

ARMC2 p.Ala655Val (c.1964C>T) is rare (popmax 0.101%, mid) (gnomAD).

What do computational predictors say about ARMC2 p.Ala655Val (c.1964C>T)?

AlphaMissense predicts likely benign (score 0.1662) — an in-silico prediction, not a clinical call.

ARMC2 p.Ala655Val

c.1964C>T · rs150814535 · VCV3129619

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1662 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.101%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1662	likely benign
REVEL	0.226	benign-leaning
SaProt	LLR -10.25	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 0.15, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 119 kb · p 0.00055 · regional, not allelic
Overall
CADD	23.4	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 0.101% Middle Eastern · 6/5,916 alleles

Filtering AF 0.0441% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0301%

Overall 0.00664% 107/1,611,838 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.101%	986
Remaining individualsnot grpmax-eligible	0.00962%	10,400
European (non-Finnish)	0.00704%	14,206
South Asian	0.0055%	18,174
Admixed American	0.00502%	19,901
African / African-American	0.004%	24,987
East Asian	0.00223%	44,854

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: ARMC2
Protein: p.Ala655Val
Coding: c.1964C>T
MANE Select: NM_032131
dbSNP: rs150814535
Type: single nucleotide variant
Location: chr6:108961620 (GRCh38)
Gene constraint: LOEUF 0.936 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.57
Residue 655: a UniProt-annotated variant site (in spgf38; uncertain significance)

Full ARMC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARMC2 c.2153-1G>C Likely pathogenic ★ same type
ARMC2 p.Asn743Asp Likely pathogenic ★ same type
ARMC2 p.Ala123Val Uncertain significance ★ ⚠ same type
ARMC2 p.Ala143Thr Uncertain significance ★ ⚠ same type
ARMC2 p.Ala231Thr Uncertain significance ★ ⚠ same type
ARMC2 p.Ala260Pro Uncertain significance ★ ⚠ same type
ARMC2 p.Ala292Asp Uncertain significance ★ ⚠ same type
ARMC2 p.Ala495Val 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/armc2-p-ala655val (accessed [today's date]).

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