Is RHOH p.Pro30Ser (c.88C>T) pathogenic?

RHOH p.Pro30Ser (c.88C>T) is classified Uncertain significance in RHOH (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-12). AlphaMissense: likely pathogenic (0.7373); Very rare (popmax 8.47e-05%, nfe); Associated with T-cell immunodeficiency with epidermodysplasia verruciformis.

What condition is associated with RHOH p.Pro30Ser (c.88C>T)?

RHOH p.Pro30Ser (c.88C>T) is associated with T-cell immunodeficiency with epidermodysplasia verruciformis (ClinVar).

How common is RHOH p.Pro30Ser (c.88C>T) in the general population?

RHOH p.Pro30Ser (c.88C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about RHOH p.Pro30Ser (c.88C>T)?

AlphaMissense predicts likely pathogenic (score 0.7373) — an in-silico prediction, not a clinical call.

RHOH p.Pro30Ser

Q: How is T-cell immunodeficiency with epidermodysplasia verruciformis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.88C>T · rs1434343798 · VCV944995

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7373 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

T-cell immunodeficiency with epidermodysplasia verruciformis

Computational evidence

Protein change
AlphaMissense	0.7373	likely pathogenic
REVEL	0.714	pathogenic-leaning
SaProt	LLR -9.57	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 358 bp · p 5.3e-09 · regional, not allelic
Overall
CADD	27.2	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,956 alleles

Overall 6.2e-05% 1/1,613,946 alleles · very rare exomes 1/1,461,834 · genomes 0/152,112 · 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: RHOH
Protein: p.Pro30Ser
Coding: c.88C>T
MANE Select: NM_004310
dbSNP: rs1434343798
Type: single nucleotide variant
Location: chr4:40243474 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI 0.25 (gnomAD)
Structure: AlphaFold pLDDT 92.81

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

Disease context

T-cell immunodeficiency with epidermodysplasia verruciformis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For T-cell immunodeficiency with epidermodysplasia verruciformis (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

RHOH p.Pro30Leu Uncertain significance ★ ⚠ same residue
RHOH p.Pro30= Likely benign ★ same residue
RHOH p.Pro30Arg Uncertain significance ★ ⚠ same residue
RHOH p.Arg157Gln Uncertain significance ★★ ⚠ same condition
RHOH p.Gly61Ser Uncertain significance ★★ ⚠ same condition
RHOH p.Ser104Gly Uncertain significance ★★ ⚠ same condition
RHOH p.Ala14= Likely benign ★★ same condition
RHOH p.Ala166= Likely benign ★★ same condition

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/rhoh-p-pro30ser (accessed [today's date]).

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