Is PMS2 p.Asp752Ala (c.2253_2255delinsCGC) pathogenic?

PMS2 p.Asp752Ala (c.22532255delinsCGC) is classified Uncertain significance in PMS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-13). No gnomAD frequency available for this variant; Associated with Hereditary nonpolyposis colorectal neoplasms.

What condition is associated with PMS2 p.Asp752Ala (c.2253_2255delinsCGC)?

PMS2 p.Asp752Ala (c.2253_2255delinsCGC) is associated with Hereditary nonpolyposis colorectal neoplasms (ClinVar).

How common is PMS2 p.Asp752Ala (c.2253_2255delinsCGC) in the general population?

PMS2 p.Asp752Ala (c.2253_2255delinsCGC) is no gnomAD frequency available for this variant (gnomAD).

PMS2 p.Asp752Ala

c.2253_2255delinsCGC · rs2128682292 · VCV1519041

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Hereditary nonpolyposis colorectal neoplasms

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	phastCons 1
Regional constraint	o/e 0.40	unconstrained · MANE · 13 kb · p 2e-20 · regional, not allelic
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

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.Asp752Ala
Coding: c.2253_2255delinsCGC
MANE Select: NM_000535
dbSNP: rs2128682292
Type: Indel
Location: chr7:5978616 (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

Similar variants

PMS2 p.Asp752Glu Uncertain significance ★ same residue
PMS2 p.His839fs Pathogenic ★★ same condition
PMS2 p.Lys130delinsCysAsnSerSerProLysCysLeuTer Pathogenic ★★ same condition
PMS2 p.Asn204Asp Uncertain significance ★★ same condition
PMS2 p.Glu411Leu Uncertain significance ★★ same condition
PMS2 p.Leu822Val Uncertain significance ★★ same condition
PMS2 p.Asn775_Trp776delinsSerTer Pathogenic ★ same condition
PMS2 p.Gln631fs 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-asp752ala (accessed [today's date]).

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