Is TRPC3 p.Ser788= (c.2364A>G) pathogenic?

TRPC3 p.Ser788= (c.2364A>G) is classified Benign/Likely benign in TRPC3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-05). Rare (popmax 0.91%, sas).

How common is TRPC3 p.Ser788= (c.2364A>G) in the general population?

TRPC3 p.Ser788= (c.2364A>G) is rare (popmax 0.91%, sas) (gnomAD).

TRPC3 p.Ser788=

c.2364A>G · rs147677309 · VCV2655062

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.91%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -9.6	GERP -4.4
Overall
CADD	0.128	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.91% South Asian · 828/91,032 alleles

Filtering AF 0.858% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.838%

Overall 0.0825% 1,332/1,613,570 alleles · rare exomes 1,249/1,461,278 · genomes 83/152,292 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.12%	90
South Asiangrpmax	0.91%	110
Remaining individualsnot grpmax-eligible	0.117%	856
Middle Eastern	0.116%	865
European (non-Finnish)	0.00771%	12,964
African / African-American	0.00267%	37,508
Admixed American	0.00167%	59,930

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: TRPC3
Protein: p.Ser788=
Coding: c.2364A>G
MANE Select: NM_001130698
dbSNP: rs147677309
Type: single nucleotide variant
Location: chr4:121902951 (GRCh38)
Gene constraint: LOEUF 0.751 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.42 · 19 PDB

Full TRPC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRPC3 p.Arg381Cys Uncertain significance ★★ same type
TRPC3 p.Arg795Gln Uncertain significance ★★ same type
TRPC3 p.Asn728Ser Uncertain significance ★★ same type
TRPC3 p.Glu901Lys Uncertain significance ★★ same type
TRPC3 p.Ile629Val Uncertain significance ★★ same type
TRPC3 p.Leu905Val Uncertain significance ★★ same type
TRPC3 p.Lys710Arg Uncertain significance ★★ same type
TRPC3 p.Pro444Ser Uncertain significance ★★ same type

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-ser788 (accessed [today's date]).

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