TRPM1 p.Asp623=
c.1869C>T · rs569549766 · VCV1093313
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0406%, sas)
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 -13 | GERP -5.4 |
| Overall | ||
| CADD | 0.283 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0406%
South Asian · 37/91,050 alleles
Filtering AF
0.0303%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0267%
Overall
0.00372%
60/1,614,080 alleles · ultra-rare
exomes 55/1,461,796 · genomes 5/152,284 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0406% | 2,461 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,835 |
| European (non-Finnish) | 0.00169% | 58,999 |
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
- TRPM1
- Protein
- p.Asp623=
- Coding
- c.1869C>T
- MANE Select
- NM_001252024
- dbSNP
- rs569549766
- Type
- single nucleotide variant
- Location
- chr15:31042169 (GRCh38)
- Gene constraint
- LOEUF 0.839 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 66.74
Similar variants
- TRPM1 p.Asp623Asn Uncertain significance ★ ⚠ same residue
- TRPM1 c.1089+1G>A Likely pathogenic ★★ same type
- TRPM1 c.2316+1G>A Pathogenic/Likely pathogenic ★★ same type
- TRPM1 c.2317-1G>C Likely pathogenic ★★ same type
- TRPM1 c.2440-2A>G Likely pathogenic ★★ same type
- TRPM1 c.2571+1G>A Likely pathogenic ★★ same type
- TRPM1 c.3127+1G>A Pathogenic/Likely pathogenic ★★ same type
- TRPM1 c.3148+1G>A Pathogenic/Likely pathogenic ★★ 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/trpm1-p-asp623 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown