PMS2 p.Asp60fs
c.176dup · rs1785429311 · VCV2694406
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
ultra-rare (gnomAD MAF 7.285e-07)
Conditions
1
Hereditary nonpolyposis colorectal neoplasms
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 3 of 15 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 2.2 | phastCons 1 |
| Region caveats | ||
| Repeat context | seg dup | · reads may not map uniquely · confidence, not pathogenicity |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
dbSNP / gnomAD
Global frequency
7.28e-05%
via dbSNP · ultra-rare
No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.
Variant & gene context
- Gene
- PMS2
- Protein
- p.Asp60fs
- Coding
- c.176dup
- MANE Select
- NM_000535
- dbSNP
- rs1785429311
- Type
- Duplication
- Location
- chr7:6004045 (GRCh38)
- Gene constraint
- LOEUF 0.898 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 71.37 · 9 PDB
- Residue 60
- a UniProt-annotated variant site (normal dna mismatch repair activity); an α-helix
Similar variants
- PMS2 p.Asp60Asn Uncertain significance ★★ ⚠ same residue
- PMS2 p.Asp60Gly Uncertain significance ★★ ⚠ same residue
- PMS2 p.Asp60Tyr Uncertain significance ★★ ⚠ same residue
- PMS2 p.Asp60Ala Uncertain significance ★ ⚠ same residue
- PMS2 p.Asp60Glu Likely benign ★★★ same residue
- PMS2 p.Arg151fs Pathogenic ★★ same condition
- PMS2 p.Arg169fs Pathogenic/Likely pathogenic ★★ same condition
- PMS2 p.Arg211fs 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-asp60fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown