Is PMS2 p.Ser260= (c.780C>T) pathogenic?

PMS2 p.Ser260= (c.780C>T) is classified Likely benign in PMS2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-25). Very rare (popmax 0.00167%, amr); Associated with Hereditary nonpolyposis colorectal neoplasms.

How common is PMS2 p.Ser260= (c.780C>T) in the general population?

PMS2 p.Ser260= (c.780C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

PMS2 p.Ser260=

Q: What condition is associated with PMS2 p.Ser260= (c.780C>T)?

PMS2 p.Ser260= (c.780C>T) is associated with Hereditary nonpolyposis colorectal neoplasms, hereditary neoplastic syndrome (ClinVar).

c.780C>T · rs1805319 · VCV183710

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 -9.7
Overall
CADD	0.006	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,716 alleles

Overall 0.000189% 3/1,590,910 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,716
African / African-American	0.00135%	74,188
European (non-Finnish)	8.62e-05%	1,159,855

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PMS2
Protein: p.Ser260=
Coding: c.780C>T
MANE Select: NM_000535
dbSNP: rs1805319
Type: single nucleotide variant
Location: chr7:5997349 (GRCh38)
Gene constraint: LOEUF 0.898 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.37 · 9 PDB
Residue 260: a turn

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: hereditary neoplastic syndrome

Similar variants

PMS2 p.Ser260Cys Uncertain significance ★★ ⚠ same residue
PMS2 p.Ser260Phe Uncertain significance ★★ ⚠ same residue
PMS2 p.Ser260Thr Uncertain significance ★★ ⚠ same residue
PMS2 p.Ser260Tyr Uncertain significance ★★ ⚠ same residue
PMS2 p.Ser260Pro Uncertain significance ★ ⚠ same residue
PMS2 p.Ser260Trp Uncertain significance ★★ same residue
PMS2 p.Ser260fs Pathogenic ★ same residue
PMS2 p.Ser260Ter 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-ser260 (accessed [today's date]).

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