Is ARMC3 p.Ala394Ser (c.1180G>T) pathogenic?

ARMC3 p.Ala394Ser (c.1180G>T) is classified Uncertain significance in ARMC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-11). AlphaMissense: likely benign (0.1648); Rare (popmax 0.61%, mid).

How common is ARMC3 p.Ala394Ser (c.1180G>T) in the general population?

ARMC3 p.Ala394Ser (c.1180G>T) is rare (popmax 0.61%, mid) (gnomAD).

What do computational predictors say about ARMC3 p.Ala394Ser (c.1180G>T)?

AlphaMissense predicts likely benign (score 0.1648) — an in-silico prediction, not a clinical call.

ARMC3 p.Ala394Ser

c.1180G>T · rs148979623 · VCV2216929

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1648 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.61%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1648	likely benign
REVEL	0.113	moderately benign-leaning
SaProt	LLR -8.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -3.3, phastCons 0.16
Regional constraint	o/e 0.92	unconstrained · MANE · 105 kb · p 0.0086 · regional, not allelic
Overall
CADD	19.28	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.61% Middle Eastern · 37/6,062 alleles

Filtering AF 0.455% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.401%

Overall 0.0305% 492/1,613,676 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.61%	164
Remaining individualsnot grpmax-eligible	0.0352%	2,840
Admixed American	0.035%	2,858
European (non-Finnish)	0.0317%	3,155
South Asian	0.0264%	3,792
African / African-American	0.0173%	5,772
Finnishnot grpmax-eligible	0.00157%	63,894

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: ARMC3
Protein: p.Ala394Ser
Coding: c.1180G>T
MANE Select: NM_173081
dbSNP: rs148979623
Type: single nucleotide variant
Location: chr10:22998152 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.81

Full ARMC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARMC3 p.Met441Ile Uncertain significance ★★ ⚠ same type
ARMC3 c.916+1G>A Uncertain significance ★ same type
ARMC3 p.Ala115Asp Uncertain significance ★ ⚠ same type
ARMC3 p.Ala118Thr Uncertain significance ★ ⚠ same type
ARMC3 p.Ala138Ser Uncertain significance ★ ⚠ same type
ARMC3 p.Ala192Ser Uncertain significance ★ ⚠ same type
ARMC3 p.Ala211Val Uncertain significance ★ ⚠ same type
ARMC3 p.Ala335Thr 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/armc3-p-ala394ser (accessed [today's date]).

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