Computational evidence
| Protein change | ||
| AlphaMissense | 0.0628 | likely benign |
|---|---|---|
| REVEL | 0.031 | moderately benign-leaning |
| SaProt | LLR -6.73 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.2 | |
| Regional constraint | o/e 1.09 | unconstrained · MANE · 22 kb · p 0.015 · regional, not allelic |
| Overall | ||
| CADD | 0.32 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 5.19% | 19 |
| Ashkenazi Jewishnot grpmax-eligible | 3.23% | 31 |
| European (non-Finnish)grpmax | 2.87% | 35 |
| Middle Eastern | 2.67% | 37 |
| Remaining individualsnot grpmax-eligible | 2.47% | 40 |
| South Asian | 2.08% | 48 |
| Amishnot grpmax-eligible | 1.86% | 54 |
| Admixed American | 1.3% | 77 |
| African / African-American | 0.568% | 176 |
Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Thr511Ala
- Coding
- c.1531A>G
- MANE Select
- NM_000535
- dbSNP
- rs2228007
- Type
- single nucleotide variant
- Location
- chr7:5987234 (GRCh38)
- Gene constraint
- LOEUF 0.898 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 71.37 · 9 PDB
- Residue 511
- the 'disordered' region; a UniProt-annotated variant site (in lynch4; benign; normal dna mismatch repair activity); a UniProt-annotated variant site (normal dna mismatch repair activity); a UniProt-annotated variant site (in)
Disease context
Lynch syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: endometrial carcinomaLynch syndrome 4hereditary neoplastic syndrome
For Lynch syndrome (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- Adult
Similar variants
- PMS2 p.Thr511Met Benign ★★★ same residue
- PMS2 p.Thr511Ser Uncertain significance ★★ ⚠ same residue
- PMS2 p.Thr511= Benign/Likely benign ★★ same residue
- PMS2 p.Thr511fs Pathogenic ★★ same residue
- PMS2 p.Thr511Val Uncertain significance ★ same residue
- PMS2 c.1144+2T>A Likely pathogenic ★★★ same condition
- PMS2 c.163+2T>C Likely pathogenic ★★★ same condition
- PMS2 c.164-2A>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-thr511ala (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown