Is PMS2 p.Ser457= (c.1371C>T) pathogenic?

PMS2 p.Ser457= (c.1371C>T) is classified Likely benign in PMS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). Absent from gnomAD v4.1; Associated with Hereditary nonpolyposis colorectal neoplasms.

What condition is associated with PMS2 p.Ser457= (c.1371C>T)?

PMS2 p.Ser457= (c.1371C>T) is associated with Hereditary nonpolyposis colorectal neoplasms (ClinVar).

How common is PMS2 p.Ser457= (c.1371C>T) in the general population?

PMS2 p.Ser457= (c.1371C>T) is absent from gnomAD v4.1 (gnomAD).

PMS2 p.Ser457=

c.1371C>T · rs1060504840 · VCV416561

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.9
Overall
CADD	0.345	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PMS2
Protein: p.Ser457=
Coding: c.1371C>T
MANE Select: NM_000535
dbSNP: rs1060504840
Type: single nucleotide variant
Location: chr7:5987394 (GRCh38)
Gene constraint: LOEUF 0.898 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.37 · 9 PDB
Residue 457: 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

Similar variants

PMS2 p.Ser457Gly Uncertain significance ★★ ⚠ same residue
PMS2 p.Ser457Arg Uncertain significance ★ ⚠ same residue
PMS2 p.Ser457Ile Uncertain significance ★ ⚠ same residue
PMS2 p.Ser457Thr Uncertain significance ★ ⚠ same residue
PMS2 c.1145-2A>G Likely pathogenic ★★ same condition
PMS2 c.164-1G>A Pathogenic/Likely pathogenic ★★ same condition
PMS2 c.164-1G>C Pathogenic/Likely pathogenic ★★ same condition
PMS2 c.2006+1G>A 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-ser457 (accessed [today's date]).

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