PMS2 p.Thr89=
c.267A>C · rs876659181 · VCV1194645
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 8.5e-05%, nfe)
Conditions
1
hereditary neoplastic syndrome
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 1.1 | phastCons 1 |
| Overall | ||
| CADD | 8.117 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.5e-05%
European (non-Finnish) · 1/1,177,096 alleles
Overall
0.000657%
1/152,138 alleles · very rare
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
- PMS2
- Protein
- p.Thr89=
- Coding
- c.267A>C
- MANE Select
- NM_000535
- dbSNP
- rs876659181
- Type
- single nucleotide variant
- Location
- chr7:6003776 (GRCh38)
- Gene constraint
- LOEUF 0.898 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 71.37 · 9 PDB
Similar variants
- PMS2 p.Thr89Ala Uncertain significance ★★ ⚠ same residue
- PMS2 p.Thr89Ile Uncertain significance ★★ ⚠ same residue
- PMS2 c.163+2T>C Likely pathogenic ★★★ same condition
- PMS2 c.164-2A>G Likely pathogenic ★★★ same condition
- PMS2 c.2007-1G>A Likely pathogenic ★★★ same condition
- PMS2 c.2174+1G>A Pathogenic ★★★ same condition
- PMS2 c.705+1G>T Likely pathogenic ★★★ same condition
- PMS2 c.989-2A>G 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/pms2-p-thr89 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown