Is TRPC5 p.Phe319= (c.957C>T) pathogenic?

TRPC5 p.Phe319= (c.957C>T) is classified Likely benign in TRPC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-01). Very rare (popmax 0.000112%, nfe).

How common is TRPC5 p.Phe319= (c.957C>T) in the general population?

TRPC5 p.Phe319= (c.957C>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

TRPC5 p.Phe319=

c.957C>T · rs1198241243 · VCV2661219

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

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 4.3	GERP -0.76, phastCons 1
Overall
CADD	8.911	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/895,386 alleles

Overall 9.11e-05% 1/1,097,815 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.Phe319=
Coding: c.957C>T
MANE Select: NM_012471
dbSNP: rs1198241243
Type: single nucleotide variant
Location: chrX:111854050 (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-phe319 (accessed [today's date]).

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