TRPM3 p.Ser63Phe
c.188C>T · rs2095596642 · VCV2635491
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00342%, amr)
Conditions
1
TRPM3-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.593 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 0.77 | unconstrained · MANE · 502 kb · p 1.1e-12 · regional, not allelic |
| Overall | ||
| CADD | 31.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00342%
Admixed American · 1/29,278 alleles
Filtering AF
0.000627%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000458%
Overall
0.000974%
12/1,231,690 alleles · very rare
exomes 10/1,112,570 · genomes 2/119,120 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00342% | 29,278 |
| European (non-Finnish) | 0.00117% | 85,575 |
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
- TRPM3
- Protein
- p.Ser63Phe
- Coding
- c.188C>T
- MANE Select
- NM_001366145
- dbSNP
- rs2095596642
- Type
- single nucleotide variant
- Location
- chr9:70864501 (GRCh38)
- Gene constraint
- LOEUF 0.48 · pLI 0.90 (gnomAD)
- Structure
- AlphaFold pLDDT 64.70 · 1 PDB
Disease context
TRPM3-related disorder
Similar variants
- TRPM3 p.Met772Val Likely pathogenic ★ same condition
- TRPM3 p.Trp1139Ser Likely pathogenic ★ same condition
- TRPM3 p.Ala408Thr Uncertain significance ★ same condition
- TRPM3 p.Ala745Val Uncertain significance ★ same condition
- TRPM3 p.Gly329Ser Uncertain significance ★ same condition
- TRPM3 p.Lys659Arg Uncertain significance ★ same condition
- TRPM3 p.Val542Ile Uncertain significance ★ same condition
- TRPM3 p.Lys1051Asn 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/trpm3-p-ser63phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown