Is TRPC5 p.Ser937Phe (c.2810C>T) pathogenic?

TRPC5 p.Ser937Phe (c.2810C>T) is classified Uncertain significance in TRPC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-11). AlphaMissense: likely benign (0.1792); Very rare (popmax 0.00424%, nfe).

How common is TRPC5 p.Ser937Phe (c.2810C>T) in the general population?

TRPC5 p.Ser937Phe (c.2810C>T) is very rare (popmax 0.00424%, nfe) (gnomAD).

What do computational predictors say about TRPC5 p.Ser937Phe (c.2810C>T)?

AlphaMissense predicts likely benign (score 0.1792) — an in-silico prediction, not a clinical call.

TRPC5 p.Ser937Phe

c.2810C>T · VCV3462040

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1792 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00424%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1792	likely benign
REVEL	0.467	indeterminate
SaProt	LLR -9.06	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 9.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 5,681 bp · p 0.061 · regional, not allelic
Overall
CADD	24.1	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 0.00424% European (non-Finnish) · 38/895,435 alleles

Filtering AF 0.00315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00346% 38/1,097,812 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.Ser937Phe
Coding: c.2810C>T
MANE Select: NM_012471
Type: single nucleotide variant
Location: chrX:111776425 (GRCh38)
Structure: AlphaFold pLDDT 73.82 · 30 PDB

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

Similar variants

TRPC5 p.Ala929Thr Uncertain significance ★ ⚠ same type
TRPC5 p.Arg120Gln Uncertain significance ★ ⚠ same type
TRPC5 p.Arg175Cys Uncertain significance ★ ⚠ same type
TRPC5 p.Arg17Cys Uncertain significance ★ ⚠ same type
TRPC5 p.Arg17His Uncertain significance ★ ⚠ same type
TRPC5 p.Arg17Leu Uncertain significance ★ ⚠ same type
TRPC5 p.Arg222Cys Uncertain significance ★ ⚠ same type
TRPC5 p.Arg263Lys 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/trpc5-p-ser937phe (accessed [today's date]).

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