Is ARMC12 p.Arg15Pro (c.44G>C) pathogenic?

ARMC12 p.Arg15Pro (c.44G>C) is classified Uncertain significance in ARMC12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely benign (0.3125); Very rare (popmax 8.47e-05%, nfe).

How common is ARMC12 p.Arg15Pro (c.44G>C) in the general population?

ARMC12 p.Arg15Pro (c.44G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ARMC12 p.Arg15Pro (c.44G>C)?

AlphaMissense predicts likely benign (score 0.3125) — an in-silico prediction, not a clinical call.

ARMC12 p.Arg15Pro

c.44G>C · VCV4643032

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3125 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3125	likely benign
REVEL	0.267	benign-leaning
SaProt	LLR -5.99	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 4.4	GERP 0.6, phastCons 0.96
Regional constraint	o/e 0.90	unconstrained · MANE · 12 kb · p 0.039 · regional, not allelic
Overall
CADD	18.29	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 8.47e-05% European (non-Finnish) · 1/1,180,034 alleles

Overall 6.84e-05% 1/1,461,872 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: ARMC12
Protein: p.Arg15Pro
Coding: c.44G>C
MANE Select: NM_001286574
Type: single nucleotide variant
Location: chr6:35737152 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.08
Residue 15: the 'interaction with tbc1d15' region

Full ARMC12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARMC12 p.Arg15Cys Uncertain significance ★ ⚠ same residue
ARMC12 c.163+10C>T Uncertain significance ★ same type
ARMC12 c.163+19G>C Uncertain significance ★ same type
ARMC12 c.163+38G>C Uncertain significance ★ same type
ARMC12 c.163+52C>G Uncertain significance ★ same type
ARMC12 c.163+54G>A Uncertain significance ★ same type
ARMC12 p.Ala104Val Uncertain significance ★ ⚠ same type
ARMC12 p.Ala27Val 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/armc12-p-arg15pro (accessed [today's date]).

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