Is RHOH p.Ser53= (c.159C>T) pathogenic?

RHOH p.Ser53= (c.159C>T) is classified Likely benign in RHOH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-30). Absent from gnomAD v4.1; Associated with T-cell immunodeficiency with epidermodysplasia verruciformis.

What condition is associated with RHOH p.Ser53= (c.159C>T)?

RHOH p.Ser53= (c.159C>T) is associated with T-cell immunodeficiency with epidermodysplasia verruciformis (ClinVar).

How common is RHOH p.Ser53= (c.159C>T) in the general population?

RHOH p.Ser53= (c.159C>T) is absent from gnomAD v4.1 (gnomAD).

RHOH p.Ser53=

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.159C>T · VCV3721905

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

T-cell immunodeficiency with epidermodysplasia verruciformis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 2.1, phastCons 1
Overall
CADD	13.14	PHRED · no single calibrated threshold — expert panels disagree

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: RHOH
Protein: p.Ser53=
Coding: c.159C>T
MANE Select: NM_004310
Type: single nucleotide variant
Location: chr4:40243545 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI 0.25 (gnomAD)
Structure: AlphaFold pLDDT 92.81
Residue 53: a UniProt-annotated variant site (in imd129; loss-of-function variant resulting in impaired t-cell differentiation; unable to rescue t-cell lymphopenia in rhoh knockout mice; no protein detected in patient cells; results in defective tcr signaling in patient cells)

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.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
RHOH p.Ala170= Benign/Likely benign ★★ same condition
RHOH p.Asp48= Benign/Likely benign ★★ same condition
RHOH p.Asp77= 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-ser53 (accessed [today's date]).

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