Is PMS2 p.Val251fs (c.750del) pathogenic?

PMS2 p.Val251fs (c.750del) is classified Pathogenic in PMS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-19). No gnomAD frequency available for this variant; Associated with Lynch syndrome 4.

What condition is associated with PMS2 p.Val251fs (c.750del)?

PMS2 p.Val251fs (c.750del) is associated with Lynch syndrome 4 (ClinVar).

How common is PMS2 p.Val251fs (c.750del) in the general population?

PMS2 p.Val251fs (c.750del) is no gnomAD frequency available for this variant (gnomAD).

How is Lynch syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

PMS2 p.Val251fs

c.750del · rs2536225095 · VCV2674259

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Lynch syndrome 4

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 7 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.084

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.Val251fs
Coding: c.750del
MANE Select: NM_000535
dbSNP: rs2536225095
Type: Deletion
Location: chr7:5997379 (GRCh38)
Gene constraint: LOEUF 0.898 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.37 · 9 PDB
Residue 251: an α-helix

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

Disease context

Lynch syndrome 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Lynch syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

PMS2 p.Val251Met Conflicting classifications of pathogenicity ★ ⚠ same residue
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
PMS2 c.537+1del Pathogenic/Likely pathogenic ★★ same condition
PMS2 c.790_803+5del Pathogenic/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-val251fs (accessed [today's date]).

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