Is RHOA p.Pro71Ser (c.211C>T) pathogenic?

RHOA p.Pro71Ser (c.211C>T) is classified Pathogenic in RHOA (ClinVar, Single submitter, 2 submitters; last evaluated 2026-05-21). AlphaMissense: likely pathogenic (0.9894); Absent from gnomAD v4.1; Associated with ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies.

How common is RHOA p.Pro71Ser (c.211C>T) in the general population?

RHOA p.Pro71Ser (c.211C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RHOA p.Pro71Ser (c.211C>T)?

AlphaMissense predicts likely pathogenic (score 0.9894) — an in-silico prediction, not a clinical call.

RHOA p.Pro71Ser

Q: What condition is associated with RHOA p.Pro71Ser (c.211C>T)?

RHOA p.Pro71Ser (c.211C>T) is associated with ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies (ClinVar).

c.211C>T · rs1575647025 · VCV801330

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9894 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies

Computational evidence

Protein change
AlphaMissense	0.9894	likely pathogenic ✓ concordant with ClinVar
REVEL	0.698	pathogenic-leaning
SaProt	LLR -14.19	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 12	phastCons 1
Regional constraint	o/e 0.11	constrained · MANE · 13 kb · p 8e-29 · regional, not allelic
Overall
CADD	29.7	PHRED · no single calibrated threshold — expert panels disagree

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: RHOA
Protein: p.Pro71Ser
Coding: c.211C>T
MANE Select: NM_001664
dbSNP: rs1575647025
Type: single nucleotide variant
Location: chr3:49368494 (GRCh38)
Gene constraint: LOEUF 0.433 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 93.80 · 131 PDB
Residue 71: the 'switch ii region; involved in rap1gds1 isoform 2 binding' region; a UniProt-annotated variant site (in edfaob; somatic mosaic variant; decreased rho protein signal transduction; decreased substrate adhesion-dependent cell spreading; decreased stress fibers assembly; decreased cytoplasmic microtubule organization); an α-helix

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

Disease context

ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RHOA p.Glu47Lys Pathogenic ★★ same condition
RHOA p.Arg70Gly Likely pathogenic ★ same condition
RHOA c.409-605G>T Uncertain significance ★ same condition
RHOA p.Ala56Val Uncertain significance ★ ⚠ same condition
RHOA p.Ter194= Uncertain significance ★ same condition
RHOA p.Ala61Thr Uncertain significance ★★ ⚠ same type
RHOA p.Val9= Benign ★★ same type
RHOA p.Ala181Thr 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/rhoa-p-pro71ser (accessed [today's date]).

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