Is TRPC5 p.Pro399His (c.1196C>A) pathogenic?

TRPC5 p.Pro399His (c.1196C>A) is classified Uncertain significance in TRPC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-07). AlphaMissense: ambiguous (0.3886); Absent from gnomAD v4.1.

How common is TRPC5 p.Pro399His (c.1196C>A) in the general population?

TRPC5 p.Pro399His (c.1196C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRPC5 p.Pro399His (c.1196C>A)?

AlphaMissense predicts ambiguous (score 0.3886) — an in-silico prediction, not a clinical call.

TRPC5 p.Pro399His

c.1196C>A · VCV3810958

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3886 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3886	ambiguous
REVEL	0.62	indeterminate
SaProt	LLR -10.85	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 131 kb · p 1e-26 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: TRPC5
Protein: p.Pro399His
Coding: c.1196C>A
MANE Select: NM_012471
Type: single nucleotide variant
Location: chrX:111853811 (GRCh38)
Structure: AlphaFold pLDDT 73.82 · 30 PDB
Residue 399: an α-helix

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-pro399his (accessed [today's date]).

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