TPM2 p.Ser206=
c.618C>A · rs370079073 · VCV1583010
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0176%, sas)
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 0.3 | GERP -3.4, phastCons 0.96 |
| Overall | ||
| CADD | 8.19 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0176%
South Asian · 16/91,076 alleles
Filtering AF
0.011%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00888%
Overall
0.000991%
16/1,614,030 alleles · ultra-rare
exomes 16/1,461,888 · genomes 0/152,142 · 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
- TPM2
- Protein
- p.Ser206=
- Coding
- c.618C>A
- MANE Select
- NM_003289
- dbSNP
- rs370079073
- Type
- single nucleotide variant
- Location
- chr9:35684753 (GRCh38)
- Gene constraint
- LOEUF 0.87 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 91.51
- Residue 206
- a modified residue (phosphoserine)
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-ser206 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown