Is TRPC3 p.Phe230Ser (c.689T>C) pathogenic?

TRPC3 p.Phe230Ser (c.689T>C) is classified Uncertain significance in TRPC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). Absent from gnomAD v4.1; Associated with spinocerebellar ataxia type 41.

What condition is associated with TRPC3 p.Phe230Ser (c.689T>C)?

TRPC3 p.Phe230Ser (c.689T>C) is associated with spinocerebellar ataxia type 41 (ClinVar).

How common is TRPC3 p.Phe230Ser (c.689T>C) in the general population?

TRPC3 p.Phe230Ser (c.689T>C) is absent from gnomAD v4.1 (gnomAD).

How is Spinocerebellar ataxia type 41 inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

TRPC3 p.Phe230Ser

c.689T>C · VCV4880941

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

spinocerebellar ataxia type 41

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.898	moderately pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 41 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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: TRPC3
Protein: p.Phe230Ser
Coding: c.689T>C
MANE Select: NM_001130698
Type: single nucleotide variant
Location: chr4:121932569 (GRCh38)
Gene constraint: LOEUF 0.751 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.42 · 19 PDB
Residue 230: a β-strand

Full TRPC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spinocerebellar ataxia type 41 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Spinocerebellar ataxia type 41 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

TRPC3 p.Pro444Ser Uncertain significance ★★ same condition
TRPC3 p.Gly39= Benign ★★ same condition
TRPC3 p.Arg762His Uncertain significance ★ same condition
TRPC3 p.Gln849Lys Uncertain significance ★ same condition
TRPC3 p.Leu739Pro Uncertain significance ★ same condition
TRPC3 p.Met852Lys Uncertain significance ★ same condition
TRPC3 p.Ser286Trp Uncertain significance ★ same condition
TRPC3 p.Thr685Ser 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/trpc3-p-phe230ser (accessed [today's date]).

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