Is TRPC5 p.Val182= (c.546G>T) pathogenic?

TRPC5 p.Val182= (c.546G>T) is classified Likely benign in TRPC5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-07-05). Very rare (popmax 0.00219%, amr); Associated with TRPC5-related disorder.

What condition is associated with TRPC5 p.Val182= (c.546G>T)?

TRPC5 p.Val182= (c.546G>T) is associated with TRPC5-related disorder (ClinVar).

How common is TRPC5 p.Val182= (c.546G>T) in the general population?

TRPC5 p.Val182= (c.546G>T) is very rare (popmax 0.00219%, amr) (gnomAD).

TRPC5 p.Val182=

c.546G>T · VCV3356082

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00219%, amr)

Conditions

TRPC5-related disorder

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 1.1	GERP -2, phastCons 1
Overall
CADD	5.474	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00219% Admixed American · 1/45,633 alleles

Overall 8.27e-05% 1/1,209,128 alleles · very rare exomes 0/1,098,108 · genomes 1/111,020 · joint denominator

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.Val182=
Coding: c.546G>T
MANE Select: NM_012471
Type: single nucleotide variant
Location: chrX:111912645 (GRCh38)
Structure: AlphaFold pLDDT 73.82 · 30 PDB
Residue 182: an α-helix

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

Disease context

TRPC5-related disorder

Similar variants

TRPC5 p.Val182Leu Uncertain significance ⚠ same residue
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

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-val182 (accessed [today's date]).

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