PMS2 p.Gln235=
c.705G>A · rs876660872 · VCV234136
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
Lynch syndrome 4
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.88 | donor loss at this position · masked 0 · deltas |
|---|---|---|
| Pangolin | Δ0.80 | loss · gain 0.04 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | phastCons 1 |
| Overall | ||
| CADD | 22.0 | 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.Gln235=
- Coding
- c.705G>A
- MANE Select
- NM_000535
- dbSNP
- rs876660872
- Type
- single nucleotide variant
- Location
- chr7:5999108 (GRCh38)
- Gene constraint
- LOEUF 0.898 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 71.37 · 9 PDB
- Residue 235
- an α-helix
Disease context
Lynch syndrome 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: hereditary neoplastic syndrome
For Lynch syndrome (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- Adult
Similar variants
- PMS2 p.Gln235Ter Pathogenic ★★★ same residue
- PMS2 p.Gln235Pro Uncertain significance ★★ ⚠ same residue
- PMS2 p.Gln235Arg Uncertain significance ★ ⚠ same residue
- PMS2 p.Gln235His Uncertain significance ★ ⚠ same residue
- PMS2 p.Gln235Glu 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-gln235 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown