Is PMS2 p.Arg764fs (c.2291_2298del) pathogenic?

PMS2 p.Arg764fs (c.22912298del) is classified Pathogenic in PMS2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-21). Associated with Hereditary nonpolyposis colorectal neoplasms.

What condition is associated with PMS2 p.Arg764fs (c.2291_2298del)?

PMS2 p.Arg764fs (c.2291_2298del) is associated with Hereditary nonpolyposis colorectal neoplasms, hereditary neoplastic syndrome (ClinVar).

PMS2 p.Arg764fs

c.2291_2298del · VCV4720102

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

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 14 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.073
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.

Variant & gene context

Gene: PMS2
Protein: p.Arg764fs
Coding: c.2291_2298del
MANE Select: NM_000535
Type: Deletion
Location: chr7:5977735 (GRCh38)
Gene constraint: LOEUF 0.898 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.37 · 9 PDB

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

Disease context

Hereditary nonpolyposis colorectal neoplasms — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

Similar variants

PMS2 p.Arg764Lys Uncertain significance ★★ ⚠ same residue
PMS2 p.Arg764Ser Uncertain significance ★★ ⚠ same residue
PMS2 p.Arg764= Benign/Likely benign ★★ same residue
PMS2 p.Arg764Gly Uncertain significance ★ ⚠ same residue
PMS2 p.Arg764Met 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

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-arg764fs (accessed [today's date]).

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