Is ARMC3 p.Ala426Val (c.1277C>T) pathogenic?

ARMC3 p.Ala426Val (c.1277C>T) is classified Uncertain significance in ARMC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-27). AlphaMissense: ambiguous (0.5089); Ultra-rare (popmax 0.0104%, nfe).

How common is ARMC3 p.Ala426Val (c.1277C>T) in the general population?

ARMC3 p.Ala426Val (c.1277C>T) is ultra-rare (popmax 0.0104%, nfe) (gnomAD).

What do computational predictors say about ARMC3 p.Ala426Val (c.1277C>T)?

AlphaMissense predicts ambiguous (score 0.5089) — an in-silico prediction, not a clinical call.

ARMC3 p.Ala426Val

c.1277C>T · rs370012088 · VCV2391438

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5089 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0104%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5089	ambiguous
REVEL	0.7	pathogenic-leaning
SaProt	LLR -10.98	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 105 kb · p 0.0086 · regional, not allelic
Overall
CADD	27.2	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 0.0104% European (non-Finnish) · 123/1,179,190 alleles

Filtering AF 0.00893% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00837%

Overall 0.00775% 125/1,612,406 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0104%	9,587
Remaining individualsnot grpmax-eligible	0.0016%	62,402
African / African-American	0.00133%	74,914

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.Ala426Val
Coding: c.1277C>T
MANE Select: NM_173081
dbSNP: rs370012088
Type: single nucleotide variant
Location: chr10:22998249 (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-ala426val (accessed [today's date]).

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