PMS2 p.Val816=
c.2448G>A · rs1583270439 · VCV1089893
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
Hereditary nonpolyposis colorectal neoplasms
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 -0.6 | phastCons 0.012 |
| Overall | ||
| CADD | 5.435 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- PMS2
- Protein
- p.Val816=
- Coding
- c.2448G>A
- MANE Select
- NM_000535
- dbSNP
- rs1583270439
- Type
- single nucleotide variant
- Location
- chr7:5973540 (GRCh38)
- Gene constraint
- LOEUF 0.898 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 71.37 · 9 PDB
- Residue 816
- a UniProt-annotated variant site (in lynch4; uncertain significance; may affect protein stability; no effect on dna mismatch repair activity in an in vitro assay, compared to wild-type)
Similar variants
- PMS2 p.Val816Glu Uncertain significance ★★ ⚠ same residue
- PMS2 p.Val816Leu Uncertain significance ★★ ⚠ same residue
- PMS2 p.Val816Met Uncertain significance ★★ ⚠ same residue
- PMS2 p.Val816Gly Uncertain significance ★ ⚠ same residue
- PMS2 p.Val816fs Pathogenic/Likely pathogenic ★★ 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
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-val816 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown