Is ARHGAP12 p.Pro138Arg (c.413C>G) pathogenic?

ARHGAP12 p.Pro138Arg (c.413C>G) is classified Uncertain significance in ARHGAP12 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-30). AlphaMissense: likely benign (0.1237); Absent from gnomAD v4.1.

How common is ARHGAP12 p.Pro138Arg (c.413C>G) in the general population?

ARHGAP12 p.Pro138Arg (c.413C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARHGAP12 p.Pro138Arg (c.413C>G)?

AlphaMissense predicts likely benign (score 0.1237) — an in-silico prediction, not a clinical call.

ARHGAP12 p.Pro138Arg

c.413C>G · VCV3310830

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1237 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1237	likely benign
REVEL	0.196	benign-leaning
SaProt	LLR -5.68	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 9.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 101 kb · p 0.038 · regional, not allelic
Overall
CADD	24.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARHGAP12
Protein: p.Pro138Arg
Coding: c.413C>G
MANE Select: NM_018287
Type: single nucleotide variant
Location: chr10:31908443 (GRCh38)
Gene constraint: LOEUF 0.681 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.68

Full ARHGAP12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP12 p.Arg6= Benign ★★ same type
ARHGAP12 p.Ala393Val Uncertain significance ★ ⚠ same type
ARHGAP12 p.Ala458Ser Uncertain significance ★ ⚠ same type
ARHGAP12 p.Ala458Val Uncertain significance ★ ⚠ same type
ARHGAP12 p.Ala491Ser Uncertain significance ★ ⚠ same type
ARHGAP12 p.Ala491Val Uncertain significance ★ ⚠ same type
ARHGAP12 p.Ala698Thr Uncertain significance ★ ⚠ same type
ARHGAP12 p.Ala753Ser 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/arhgap12-p-pro138arg (accessed [today's date]).

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