TRPC3 p.Ala99=
c.297C>G · rs13121031 · VCV2135328
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 11.6%, nfe) — too common for a highly-penetrant pathogenic allele
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 -0.16 | GERP -2.9, phastCons 0.056 |
| Overall | ||
| CADD | 8.416 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
11.6%
European (non-Finnish) · 136,440/1,179,492 alleles
Filtering AF
11.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 11.5%
Overall
10.1%
163,609/1,613,080 alleles · common
exomes 152,173/1,460,762 · genomes 11,436/152,318 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 11.6% | 9 |
| Finnishnot grpmax-eligible | 11.3% | 9 |
| Middle Eastern | 11.3% | 9 |
| Remaining individualsnot grpmax-eligible | 9.34% | 11 |
| South Asian | 7.71% | 13 |
| Amishnot grpmax-eligible | 6.03% | 17 |
| Admixed American | 5.87% | 17 |
| Ashkenazi Jewishnot grpmax-eligible | 4.76% | 21 |
| African / African-American | 1.92% | 52 |
| East Asian | 0.0111% | 8,973 |
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.Ala99=
- Coding
- c.297C>G
- MANE Select
- NM_001130698
- dbSNP
- rs13121031
- Type
- single nucleotide variant
- Location
- chr4:121932961 (GRCh38)
- Gene constraint
- LOEUF 0.751 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.42 · 19 PDB
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-ala99 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown