Is TRPC5 p.Ser925Pro (c.2773T>C) pathogenic?

TRPC5 p.Ser925Pro (c.2773T>C) is classified Uncertain significance in TRPC5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-08-29). AlphaMissense: likely benign (0.081); Very rare (popmax 9.11e-05%); Associated with TRPC5-related disorder.

What condition is associated with TRPC5 p.Ser925Pro (c.2773T>C)?

TRPC5 p.Ser925Pro (c.2773T>C) is associated with TRPC5-related disorder (ClinVar).

How common is TRPC5 p.Ser925Pro (c.2773T>C) in the general population?

TRPC5 p.Ser925Pro (c.2773T>C) is very rare (popmax 9.11e-05%) (gnomAD).

What do computational predictors say about TRPC5 p.Ser925Pro (c.2773T>C)?

AlphaMissense predicts likely benign (score 0.081) — an in-silico prediction, not a clinical call.

TRPC5 p.Ser925Pro

c.2773T>C · VCV3346025

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.081 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 9.11e-05%)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

TRPC5-related disorder

Computational evidence

Protein change
AlphaMissense	0.081	likely benign
REVEL	0.354	indeterminate
SaProt	LLR -7.08	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 5,681 bp · p 0.061 · regional, not allelic
Overall
CADD	22.3	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 9.11e-05%

Overall 9.11e-05% 1/1,097,671 alleles · very rare

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: TRPC5
Protein: p.Ser925Pro
Coding: c.2773T>C
MANE Select: NM_012471
Type: single nucleotide variant
Location: chrX:111776462 (GRCh38)
Structure: AlphaFold pLDDT 73.82 · 30 PDB

Full TRPC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

TRPC5-related disorder

Similar variants

TRPC5 p.Arg222Cys Uncertain significance ★ ⚠ same condition
TRPC5 p.Gln914Glu Uncertain significance ★ ⚠ same condition
TRPC5 p.Lys7Gln Uncertain significance ★ ⚠ same condition
TRPC5 p.Ala912Thr Uncertain significance ⚠ same condition
TRPC5 p.Arg120Trp Uncertain significance ⚠ same condition
TRPC5 p.Arg191His Uncertain significance ⚠ same condition
TRPC5 p.Arg260Trp Uncertain significance ⚠ same condition
TRPC5 p.Arg324Gln Uncertain significance ⚠ 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/trpc5-p-ser925pro (accessed [today's date]).

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