Is PMS2 p.Lys413Arg (c.1238_1239delinsGG) pathogenic?

PMS2 p.Lys413Arg (c.12381239delinsGG) is classified Conflicting classifications of pathogenicity in PMS2 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-19). No gnomAD frequency available for this variant; Associated with Hereditary nonpolyposis colorectal neoplasms.

How common is PMS2 p.Lys413Arg (c.1238_1239delinsGG) in the general population?

PMS2 p.Lys413Arg (c.1238_1239delinsGG) is no gnomAD frequency available for this variant (gnomAD).

PMS2 p.Lys413Arg

Q: What condition is associated with PMS2 p.Lys413Arg (c.1238_1239delinsGG)?

PMS2 p.Lys413Arg (c.1238_1239delinsGG) is associated with Hereditary nonpolyposis colorectal neoplasms, Lynch syndrome 4, hereditary neoplastic syndrome (ClinVar).

c.1238_1239delinsGG · rs587780041 · VCV127756

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

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 -0.5
Regional constraint	o/e 1.09	unconstrained · MANE · 22 kb · p 0.015 · 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.Lys413Arg
Coding: c.1238_1239delinsGG
MANE Select: NM_000535
dbSNP: rs587780041
Type: Indel
Location: chr7:5987526 (GRCh38)
Gene constraint: LOEUF 0.898 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.37 · 9 PDB
Residue 413: the 'disordered' region

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: Lynch syndrome 4 hereditary neoplastic syndrome

Similar variants

PMS2 p.Lys413Gly Uncertain significance ★ same residue
PMS2 p.Lys413Asn Uncertain significance ★★ ⚠ same residue
PMS2 p.Lys413fs Pathogenic ★ same residue
PMS2 p.Lys413= Conflicting classifications of pathogenicity ★ same residue
PMS2 p.Lys413_Asp414insLys Uncertain significance ★ same residue
PMS2 p.Lys413Glu Uncertain significance ★ ⚠ same residue
PMS2 p.Lys413Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
PMS2 p.Lys413del Pathogenic same residue

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-lys413arg (accessed [today's date]).

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