Is TRPC3 p.Val474fs (c.1419del) pathogenic?

TRPC3 p.Val474fs (c.1419del) is classified Pathogenic in TRPC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-04). No gnomAD frequency available for this variant; Associated with spinocerebellar ataxia type 41.

What condition is associated with TRPC3 p.Val474fs (c.1419del)?

TRPC3 p.Val474fs (c.1419del) is associated with spinocerebellar ataxia type 41 (ClinVar).

How common is TRPC3 p.Val474fs (c.1419del) in the general population?

TRPC3 p.Val474fs (c.1419del) is no gnomAD frequency available for this variant (gnomAD).

How is Spinocerebellar ataxia type 41 inherited?

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

TRPC3 p.Val474fs

c.1419del · rs2149125943 · VCV1027487

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

spinocerebellar ataxia type 41

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TRPC3
Protein: p.Val474fs
Coding: c.1419del
MANE Select: NM_001130698
dbSNP: rs2149125943
Type: Deletion
Location: chr4:121912016 (GRCh38)
Gene constraint: LOEUF 0.751 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.42 · 19 PDB
Residue 474: 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.Val474= Likely benign ★ same residue
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

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-val474fs (accessed [today's date]).

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