Is TRPC3 p.Ser286Trp (c.857C>G) pathogenic?

TRPC3 p.Ser286Trp (c.857C>G) is classified Uncertain significance in TRPC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-22). Very rare (popmax 0.000339%, nfe); Associated with spinocerebellar ataxia type 41.

What condition is associated with TRPC3 p.Ser286Trp (c.857C>G)?

TRPC3 p.Ser286Trp (c.857C>G) is associated with spinocerebellar ataxia type 41 (ClinVar).

How common is TRPC3 p.Ser286Trp (c.857C>G) in the general population?

TRPC3 p.Ser286Trp (c.857C>G) is very rare (popmax 0.000339%, nfe) (gnomAD).

How is Spinocerebellar ataxia type 41 inherited?

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

TRPC3 p.Ser286Trp

c.857C>G · rs774832979 · VCV2437338

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

spinocerebellar ataxia type 41

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.845	moderately pathogenic-leaning
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 0.84	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

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,018 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,614,124 alleles · very rare exomes 4/1,461,848 · genomes 0/152,276 · 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: TRPC3
Protein: p.Ser286Trp
Coding: c.857C>G
MANE Select: NM_001130698
dbSNP: rs774832979
Type: single nucleotide variant
Location: chr4:121932401 (GRCh38)
Gene constraint: LOEUF 0.751 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.42 · 19 PDB
Residue 286: an α-helix

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.Phe230Ser 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-ser286trp (accessed [today's date]).

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