Is TRPC5 p.Thr603= (c.1809C>G) pathogenic?

TRPC5 p.Thr603= (c.1809C>G) is classified Benign in TRPC5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-02). Low-frequency (popmax 1.75%, nfe); Associated with TRPC5-related disorder.

What condition is associated with TRPC5 p.Thr603= (c.1809C>G)?

TRPC5 p.Thr603= (c.1809C>G) is associated with TRPC5-related disorder (ClinVar).

How common is TRPC5 p.Thr603= (c.1809C>G) in the general population?

TRPC5 p.Thr603= (c.1809C>G) is low-frequency (popmax 1.75%, nfe) (gnomAD).

TRPC5 p.Thr603=

c.1809C>G · rs61729630 · VCV3055303

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.75%, nfe)

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 -0.076	GERP -4.3, phastCons 0.09
Overall
CADD	2.477	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.75% European (non-Finnish) · 15,632/894,473 alleles

Filtering AF 1.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.72%

Overall 1.44% 17,472/1,209,331 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.75%	57
Ashkenazi Jewishnot grpmax-eligible	1.29%	78
Middle Eastern	1.26%	79
Remaining individualsnot grpmax-eligible	1.25%	80
Finnishnot grpmax-eligible	0.613%	163
Admixed American	0.564%	177
South Asian	0.463%	216
African / African-American	0.176%	567

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.Thr603=
Coding: c.1809C>G
MANE Select: NM_012471
dbSNP: rs61729630
Type: single nucleotide variant
Location: chrX:111835008 (GRCh38)
Structure: AlphaFold pLDDT 73.82 · 30 PDB
Residue 603: 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.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
TRPC5 p.Arg324Gln 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-thr603 (accessed [today's date]).

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