Is TRPC5 p.Leu20= (c.58C>T) pathogenic?

TRPC5 p.Leu20= (c.58C>T) is classified Likely benign in TRPC5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-19). Rare (popmax 0.597%, mid); Associated with TRPC5-related disorder.

What condition is associated with TRPC5 p.Leu20= (c.58C>T)?

TRPC5 p.Leu20= (c.58C>T) is associated with TRPC5-related disorder (ClinVar).

How common is TRPC5 p.Leu20= (c.58C>T) in the general population?

TRPC5 p.Leu20= (c.58C>T) is rare (popmax 0.597%, mid) (gnomAD).

TRPC5 p.Leu20=

c.58C>T · rs148777982 · VCV3037643

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.597%, mid)

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 1.8	GERP -1.1, phastCons 0.99
Overall
CADD	2.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.597% Middle Eastern · 26/4,354 alleles

Filtering AF 0.418% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.362%

Overall 0.136% 1,643/1,210,100 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.597%	167
Admixed American	0.43%	232
African / African-American	0.316%	316
Remaining individualsnot grpmax-eligible	0.279%	358
Ashkenazi Jewishnot grpmax-eligible	0.254%	393
European (non-Finnish)	0.117%	854
South Asian	0.00352%	28,372

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.Leu20=
Coding: c.58C>T
MANE Select: NM_012471
dbSNP: rs148777982
Type: single nucleotide variant
Location: chrX:111952363 (GRCh38)
Structure: AlphaFold pLDDT 73.82 · 30 PDB

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-leu20 (accessed [today's date]).

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