TPM2 p.Val268=
c.804C>T · VCV4903088
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
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 | GERP 0.86, phastCons 1 |
| Overall | ||
| CADD | 20.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,868 alleles
Filtering AF
0.000359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00026%
Overall
0.000681%
11/1,614,142 alleles · very rare
exomes 11/1,461,862 · genomes 0/152,280 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,868 |
| South Asian | 0.0011% | 91,082 |
| European (non-Finnish) | 0.000763% | 131,114 |
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
- TPM2
- Protein
- p.Val268=
- Coding
- c.804C>T
- MANE Select
- NM_003289 · reported on NM_213674
- Type
- single nucleotide variant
- Location
- chr9:35682132 (GRCh38)
- Gene constraint
- LOEUF 0.87 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 91.51
Similar variants
- TPM2 p.Ala155Thr Pathogenic/Likely pathogenic ★★ same type
- TPM2 p.Arg133Trp Pathogenic ★★ same type
- TPM2 p.Gln24Ter Pathogenic/Likely pathogenic ★★ same type
- TPM2 p.Gln9Pro Likely pathogenic ★★ same type
- TPM2 p.Glu117Lys Pathogenic/Likely pathogenic ★★ same type
- TPM2 p.Glu145Lys Likely pathogenic ★★ same type
- TPM2 p.Glu187Lys Pathogenic/Likely pathogenic ★★ same type
- TPM2 p.Lys128Glu 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/tpm2-p-val268 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown