Is TRPC5 p.Ile18= (c.54C>T) pathogenic?

TRPC5 p.Ile18= (c.54C>T) is classified Likely benign in TRPC5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-02-17). Rare (popmax 0.136%, afr); Associated with TRPC5-related disorder.

What condition is associated with TRPC5 p.Ile18= (c.54C>T)?

TRPC5 p.Ile18= (c.54C>T) is associated with TRPC5-related disorder (ClinVar).

How common is TRPC5 p.Ile18= (c.54C>T) in the general population?

TRPC5 p.Ile18= (c.54C>T) is rare (popmax 0.136%, afr) (gnomAD).

TRPC5 p.Ile18=

c.54C>T · rs142387288 · VCV3051440

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.136%, afr)

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 -0.028	GERP -3.5, phastCons 0.21
Overall
CADD	1.288	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.136% African / African-American · 78/57,199 alleles

Filtering AF 0.112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.103%

Overall 0.00694% 84/1,209,981 alleles · rare exomes 35/1,097,991 · genomes 49/111,990 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.136%	733
Admixed American	0.00656%	15,250
Remaining individualsnot grpmax-eligible	0.0063%	15,863

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.Ile18=
Coding: c.54C>T
MANE Select: NM_012471
dbSNP: rs142387288
Type: single nucleotide variant
Location: chrX:111952367 (GRCh38)
Structure: AlphaFold pLDDT 73.82 · 30 PDB
Residue 18: a β-strand

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-ile18 (accessed [today's date]).

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