Is PMS2 p.Phe291fs (c.873del) pathogenic?

PMS2 p.Phe291fs (c.873del) is classified Pathogenic/Likely pathogenic in PMS2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-11-10). No gnomAD frequency available for this variant; Associated with hereditary nonpolyposis colon cancer.

What condition is associated with PMS2 p.Phe291fs (c.873del)?

PMS2 p.Phe291fs (c.873del) is associated with hereditary nonpolyposis colon cancer, Lynch syndrome 4, hereditary neoplastic syndrome (ClinVar).

How common is PMS2 p.Phe291fs (c.873del) in the general population?

PMS2 p.Phe291fs (c.873del) is no gnomAD frequency available for this variant (gnomAD).

PMS2 p.Phe291fs

c.873del · rs1261282733 · VCV585225

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary nonpolyposis colon cancer

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 8 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.4	phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PMS2
Protein: p.Phe291fs
Coding: c.873del
MANE Select: NM_000535
dbSNP: rs1261282733
Type: Deletion
Location: chr7:5995564 (GRCh38)
Gene constraint: LOEUF 0.898 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.37 · 9 PDB
Residue 291: a β-strand

Full PMS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary nonpolyposis colon cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Lynch syndrome 4 hereditary neoplastic syndrome

Similar variants

PMS2 p.Phe291= Conflicting classifications of pathogenicity ★ same residue
PMS2 p.Phe291Leu Uncertain significance ★ ⚠ same residue
PMS2 c.989-296_1144+706del Pathogenic ★★★ same condition
PMS2 p.Glu180_Tyr181insTer Pathogenic ★★★ same condition
PMS2 p.Leu731fs Pathogenic ★★★ same condition
PMS2 p.Phe788fs Pathogenic ★★★ same condition
PMS2 c.1144+1del Pathogenic/Likely pathogenic ★★ same condition
PMS2 c.2006_2006+4del 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-phe291fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown