PMS2 p.Pro247=
c.741T>A · rs2128787882 · VCV1758847
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.57e-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 3.3 | phastCons 1 |
| Overall | ||
| CADD | 14.42 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.57e-05%
European (non-Finnish) · 1/1,167,464 alleles
Overall
6.26e-05%
1/1,598,168 alleles · very rare
exomes 1/1,447,594 · genomes 0/150,574 · 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
- PMS2
- Protein
- p.Pro247=
- Coding
- c.741T>A
- MANE Select
- NM_000535
- dbSNP
- rs2128787882
- Type
- single nucleotide variant
- Location
- chr7:5997388 (GRCh38)
- Gene constraint
- LOEUF 0.898 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 71.37 · 9 PDB
- Residue 247
- an α-helix
Similar variants
- PMS2 p.Pro247Ala Uncertain significance ★★ ⚠ same residue
- PMS2 p.Pro247Arg Uncertain significance ★★ ⚠ same residue
- PMS2 p.Pro247Leu Uncertain significance ★★ ⚠ same residue
- PMS2 p.Pro247Ser Uncertain significance ★★ ⚠ same residue
- PMS2 p.Pro247Thr Uncertain significance ★★ ⚠ same residue
- PMS2 p.Pro247_Ser248insTer Pathogenic ★★ same residue
- PMS2 p.Pro247fs Pathogenic ★★ same residue
- PMS2 c.163+2T>C 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-pro247 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown