Is TRPC3 p.Ser706= (c.2118C>A) pathogenic?

TRPC3 p.Ser706= (c.2118C>A) is classified Likely benign in TRPC3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.086%, nfe).

How common is TRPC3 p.Ser706= (c.2118C>A) in the general population?

TRPC3 p.Ser706= (c.2118C>A) is ultra-rare (popmax 0.086%, nfe) (gnomAD).

TRPC3 p.Ser706=

c.2118C>A · rs112487014 · VCV2068033

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.086%, nfe)

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 -4.8	GERP -4.4
Overall
CADD	0.471	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.086% European (non-Finnish) · 1,010/1,174,366 alleles

Filtering AF 0.0815% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0798%

Overall 0.0674% 1,077/1,598,114 alleles · ultra-rare exomes 1,029/1,446,046 · genomes 48/152,068 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0907%	1,103
European (non-Finnish)grpmax	0.086%	1,163
African / African-American	0.0122%	8,214
Admixed American	0.00359%	27,890

Remaining individuals 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.Ser706=
Coding: c.2118C>A
MANE Select: NM_001130698
dbSNP: rs112487014
Type: single nucleotide variant
Location: chr4:121904457 (GRCh38)
Gene constraint: LOEUF 0.751 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.42 · 19 PDB
Residue 706: an α-helix

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-ser706 (accessed [today's date]).

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