TPM2 p.Val64=
c.192G>A · rs1382163428 · VCV1097481
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
Conditions
1
arthrogryposis, distal, type 1A
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 1.8 | GERP -2.9, phastCons 1 |
| Overall | ||
| CADD | 10.67 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,948 alleles
Filtering AF
0.000443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000186%
3/1,614,098 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,474 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
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.Val64=
- Coding
- c.192G>A
- MANE Select
- NM_003289
- dbSNP
- rs1382163428
- Type
- single nucleotide variant
- Location
- chr9:35689194 (GRCh38)
- Gene constraint
- LOEUF 0.87 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 91.51
- Residue 64
- the 'disordered' region
Similar variants
- TPM2 p.Ala155Thr Pathogenic/Likely pathogenic ★★ same condition
- TPM2 p.Arg133Trp Pathogenic ★★ same condition
- TPM2 p.Gln24Ter Pathogenic/Likely pathogenic ★★ same condition
- TPM2 p.Gln9Pro Likely pathogenic ★★ same condition
- TPM2 p.Glu117Lys Pathogenic/Likely pathogenic ★★ same condition
- TPM2 p.Lys128Glu Likely pathogenic ★★ same condition
- TPM2 p.Tyr261Cys Pathogenic/Likely pathogenic ★★ same condition
- TPM2 c.240+5G>T 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/tpm2-p-val64 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown