Is TRPC5 p.Ser798fs (c.2393_2394del) pathogenic?

TRPC5 p.Ser798fs (c.23932394del) is classified Uncertain significance in TRPC5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-15). Very rare (popmax 0.00173%, afr); Associated with TRPC5-related disorder.

What condition is associated with TRPC5 p.Ser798fs (c.2393_2394del)?

TRPC5 p.Ser798fs (c.2393_2394del) is associated with TRPC5-related disorder (ClinVar).

How common is TRPC5 p.Ser798fs (c.2393_2394del) in the general population?

TRPC5 p.Ser798fs (c.2393_2394del) is very rare (popmax 0.00173%, afr) (gnomAD).

TRPC5 p.Ser798fs

c.2393_2394del · VCV3358323

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00173%, afr)

Conditions

TRPC5-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00173% African / African-American · 1/57,807 alleles

Filtering AF 0.000241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000158%

Overall 0.000578% 7/1,211,574 alleles · very rare exomes 7/1,097,924 · genomes 0/113,650 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00173%	57,807
European (non-Finnish)	0.00067%	149,246

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.Ser798fs
Coding: c.2393_2394del
MANE Select: NM_012471
Type: Microsatellite
Location: chrX:111776841 (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.Asn679del Uncertain significance same condition
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

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-ser798fs (accessed [today's date]).

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