Is ARMC10 p.Ser166Arg (c.496A>C) pathogenic?

ARMC10 p.Ser166Arg (c.496A>C) is classified Uncertain significance in ARMC10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely pathogenic (0.9846); Very rare (popmax 0.00136%, afr).

How common is ARMC10 p.Ser166Arg (c.496A>C) in the general population?

ARMC10 p.Ser166Arg (c.496A>C) is very rare (popmax 0.00136%, afr) (gnomAD).

What do computational predictors say about ARMC10 p.Ser166Arg (c.496A>C)?

AlphaMissense predicts likely pathogenic (score 0.9846) — an in-silico prediction, not a clinical call.

ARMC10 p.Ser166Arg

c.496A>C · VCV4146384

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9846 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9846	likely pathogenic · top 1% in ARMC10
REVEL	0.676	pathogenic-leaning
SaProt	LLR -16.78	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 15 kb · p 0.0097 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00136% African / African-American · 1/73,268 alleles

Overall 0.000657% 1/152,138 alleles · very rare

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: ARMC10
Protein: p.Ser166Arg
Coding: c.496A>C
MANE Select: NM_031905
Type: single nucleotide variant
Location: chr7:103086732 (GRCh38)
Gene constraint: LOEUF 1.341 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.88

Full ARMC10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARMC10 p.Ala126Pro Uncertain significance ★ ⚠ same type
ARMC10 p.Ala132Ser Uncertain significance ★ ⚠ same type
ARMC10 p.Ala198Thr Uncertain significance ★ ⚠ same type
ARMC10 p.Ala298Gly Uncertain significance ★ ⚠ same type
ARMC10 p.Ala330Gly Uncertain significance ★ ⚠ same type
ARMC10 p.Ala7Gly Uncertain significance ★ ⚠ same type
ARMC10 p.Arg279Gln Uncertain significance ★ ⚠ same type
ARMC10 p.Arg33Trp 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/armc10-p-ser166arg (accessed [today's date]).

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