Is TRPV2 p.Pro4Ser (c.10C>T) pathogenic?

TRPV2 p.Pro4Ser (c.10C>T) is classified Uncertain significance in TRPV2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: likely benign (0.0629); Very rare (popmax 0.00266%, afr).

How common is TRPV2 p.Pro4Ser (c.10C>T) in the general population?

TRPV2 p.Pro4Ser (c.10C>T) is very rare (popmax 0.00266%, afr) (gnomAD).

What do computational predictors say about TRPV2 p.Pro4Ser (c.10C>T)?

AlphaMissense predicts likely benign (score 0.0629) — an in-silico prediction, not a clinical call.

TRPV2 p.Pro4Ser

c.10C>T · VCV4599726

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0629 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00266%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0629	likely benign
REVEL	0.264	benign-leaning
SaProt	LLR -5.69	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 0.67	GERP 0.78, phastCons 0.005
Regional constraint	o/e 0.83	unconstrained · MANE · 19 kb · p 1.8e-07 · regional, not allelic
Overall
CADD	11.48	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

Grpmax group 0.00266% African / African-American · 2/75,062 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,614,170 alleles · very rare exomes 1/1,461,860 · genomes 2/152,310 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00266%	37,531
European (non-Finnish)	8.47e-05%	1,180,012

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: TRPV2
Protein: p.Pro4Ser
Coding: c.10C>T
MANE Select: NM_016113
Type: single nucleotide variant
Location: chr17:16417678 (GRCh38)
Gene constraint: LOEUF 0.785 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.85 · 4 PDB
Residue 4: the 'required for interaction with slc50a1' region; the 'disordered' region

Full TRPV2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRPV2 p.Pro4Leu Uncertain significance ★ ⚠ same residue
TRPV2 p.Ala236Ser Uncertain significance ★ ⚠ same type
TRPV2 p.Ala236Thr Uncertain significance ★ ⚠ same type
TRPV2 p.Ala276Ser Uncertain significance ★ ⚠ same type
TRPV2 p.Ala278Gly Uncertain significance ★ ⚠ same type
TRPV2 p.Ala502Thr Uncertain significance ★ ⚠ same type
TRPV2 p.Ala51Thr Uncertain significance ★ ⚠ same type
TRPV2 p.Ala550Thr 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/trpv2-p-pro4ser (accessed [today's date]).

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