Is PMS2 p.Cys653fs (c.1957del) pathogenic?

PMS2 p.Cys653fs (c.1957del) is classified Pathogenic in PMS2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-04-28). No gnomAD frequency available for this variant; Associated with hereditary neoplastic syndrome.

What condition is associated with PMS2 p.Cys653fs (c.1957del)?

PMS2 p.Cys653fs (c.1957del) is associated with hereditary neoplastic syndrome, Lynch syndrome (ClinVar).

How common is PMS2 p.Cys653fs (c.1957del) in the general population?

PMS2 p.Cys653fs (c.1957del) is no gnomAD frequency available for this variant (gnomAD).

PMS2 p.Cys653fs

c.1957del · rs2535706177 · VCV1783334

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

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 11 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	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

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.Cys653fs
Coding: c.1957del
MANE Select: NM_000535
dbSNP: rs2535706177
Type: Deletion
Location: chr7:5986808 (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 neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Lynch syndrome

Similar variants

PMS2 c.1145-1350_*20545del Pathogenic ★★★ same condition
PMS2 c.1145-?_2174+?del Pathogenic ★★★ same condition
PMS2 c.2276-113_2445+1596del Pathogenic ★★★ same condition
PMS2 c.2276-91_2445+790del Pathogenic ★★★ same condition
PMS2 c.24-?_163+?del Pathogenic ★★★ same condition
PMS2 c.354-?_803+?del Pathogenic ★★★ same condition
PMS2 c.354-?_(*160_? Pathogenic ★★★ same condition
PMS2 c.538-478_705+456del 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-cys653fs (accessed [today's date]).

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