TPM1 p.Ser245=
c.735A>G · rs771961466 · VCV626829
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
Conditions
2
Cardiovascular phenotype
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 1.5 | GERP -1.9, phastCons 1 |
| Overall | ||
| CADD | 8.013 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,180,046 alleles
Overall
6.19e-05%
1/1,614,268 alleles · very rare
exomes 1/1,461,886 · genomes 0/152,382 · joint denominator
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
- TPM1
- Protein
- p.Ser245=
- Coding
- c.735A>G
- MANE Select
- NM_001018005
- dbSNP
- rs771961466
- Type
- single nucleotide variant
- Location
- chr15:63062608 (GRCh38)
- Gene constraint
- LOEUF 0.757 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 91.67 · 14 PDB
Similar variants
- TPM1 p.Ser245Leu Uncertain significance same residue
- TPM1 p.Ala183Val Uncertain significance ★★★ ⚠ same condition
- TPM1 p.Met281Thr Uncertain significance ★★★ ⚠ same condition
- TPM1 p.Lys266Arg Likely benign ★★★ ⚠ same condition
- TPM1 p.Thr282Ser Benign ★★★ same condition
- TPM1 p.Asp159Asn Pathogenic/Likely pathogenic ★★ same condition
- TPM1 p.Asp175Asn Pathogenic ★★ same condition
- TPM1 p.Glu192Lys Pathogenic/Likely pathogenic ★★ 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/tpm1-p-ser245 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown