Is RHOC p.Val11Phe (c.31G>T) pathogenic?

RHOC p.Val11Phe (c.31G>T) is classified Uncertain significance in RHOC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). AlphaMissense: likely pathogenic (0.9926); Very rare (popmax 0.00153%, nfe).

How common is RHOC p.Val11Phe (c.31G>T) in the general population?

RHOC p.Val11Phe (c.31G>T) is very rare (popmax 0.00153%, nfe) (gnomAD).

What do computational predictors say about RHOC p.Val11Phe (c.31G>T)?

AlphaMissense predicts likely pathogenic (score 0.9926) — an in-silico prediction, not a clinical call.

RHOC p.Val11Phe

c.31G>T · VCV3945548

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9926 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00153%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9926	likely pathogenic
REVEL	0.886	moderately pathogenic-leaning
SaProt	LLR -15.29	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 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 1,231 bp · p 1.5e-09 · regional, not allelic
Overall
CADD	33.0	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 0.00153% European (non-Finnish) · 18/1,179,534 alleles

Filtering AF 0.000954% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00112% 18/1,612,412 alleles · very rare exomes 17/1,460,266 · genomes 1/152,146 · 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: RHOC
Protein: p.Val11Phe
Coding: c.31G>T
MANE Select: NM_175744
Type: single nucleotide variant
Location: chr1:112703769 (GRCh38)
Gene constraint: LOEUF 1.024 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.36 · 4 PDB
Residue 11: a β-strand

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

Similar variants

RHOC p.Val11Ile Uncertain significance ★ ⚠ same residue
RHOC p.Ala148Val Uncertain significance ★ ⚠ same type
RHOC p.Arg140Trp Uncertain significance ★ same type
RHOC p.Arg150Pro Uncertain significance ★ ⚠ same type
RHOC p.Arg182Cys Uncertain significance ★ same type
RHOC p.Arg182His Uncertain significance ★ ⚠ same type
RHOC p.Gln180His Uncertain significance ★ ⚠ same type
RHOC p.Ile113Met 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/rhoc-p-val11phe (accessed [today's date]).

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