Is ARMC10 p.Pro111Ser (c.331C>T) pathogenic?

ARMC10 p.Pro111Ser (c.331C>T) is classified Uncertain significance in ARMC10 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). AlphaMissense: likely benign (0.141); Very rare (popmax 0.00133%, afr).

How common is ARMC10 p.Pro111Ser (c.331C>T) in the general population?

ARMC10 p.Pro111Ser (c.331C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ARMC10 p.Pro111Ser (c.331C>T)?

AlphaMissense predicts likely benign (score 0.141) — an in-silico prediction, not a clinical call.

ARMC10 p.Pro111Ser

c.331C>T · rs2538563258 · VCV2213170

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.141 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.141	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -7.29	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 1.8	GERP 0.09, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 15 kb · p 0.0097 · regional, not allelic
Overall
CADD	21.0	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 0.00133% African / African-American · 1/75,064 alleles

Overall 6.2e-05% 1/1,614,146 alleles · very rare exomes 1/1,461,790 · genomes 0/152,356 · joint denominator

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.Pro111Ser
Coding: c.331C>T
MANE Select: NM_031905
dbSNP: rs2538563258
Type: single nucleotide variant
Location: chr7:103083768 (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-pro111ser (accessed [today's date]).

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