Is PMS2 p.Ser791= (c.2373C>T) pathogenic?

PMS2 p.Ser791= (c.2373C>T) is classified Benign/Likely benign in PMS2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-28). Very rare (popmax 0.0054%, afr); Associated with mismatch repair cancer syndrome 4.

What condition is associated with PMS2 p.Ser791= (c.2373C>T)?

PMS2 p.Ser791= (c.2373C>T) is associated with mismatch repair cancer syndrome 4, Lynch syndrome 4, hereditary neoplastic syndrome (ClinVar).

How common is PMS2 p.Ser791= (c.2373C>T) in the general population?

PMS2 p.Ser791= (c.2373C>T) is very rare (popmax 0.0054%, afr) (gnomAD).

PMS2 p.Ser791=

Q: How is Constitutional mismatch repair deficiency syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.2373C>T · rs864622765 · VCV221164

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0054%, afr)

Conditions

mismatch repair cancer syndrome 4

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 -2
Overall
CADD	1.534	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0054% African / African-American · 4/74,110 alleles

Filtering AF 0.00176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00105%

Overall 0.00181% 29/1,605,188 alleles · very rare exomes 27/1,455,230 · genomes 2/149,958 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0054%	18,528
East Asian	0.00449%	22,261
European (non-Finnish)	0.00179%	55,917
Remaining individualsnot grpmax-eligible	0.00161%	62,160
South Asian	0.0011%	90,574

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.Ser791=
Coding: c.2373C>T
MANE Select: NM_000535
dbSNP: rs864622765
Type: single nucleotide variant
Location: chr7:5977660 (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

mismatch repair cancer syndrome 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Lynch syndrome 4 hereditary neoplastic syndrome

For Constitutional mismatch repair deficiency syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

PMS2 p.Ser791Asn Uncertain significance ★★ ⚠ same residue
PMS2 p.Ser791Thr Uncertain significance ★★ ⚠ same residue
PMS2 p.Ser791fs Pathogenic ★ same residue
PMS2 p.Ser791Arg Uncertain significance ★ ⚠ same residue
PMS2 c.1144+2T>A Likely pathogenic ★★★ same condition
PMS2 c.163+2T>C Likely pathogenic ★★★ same condition
PMS2 c.164-2A>G Likely pathogenic ★★★ same condition
PMS2 c.2007-1G>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-ser791 (accessed [today's date]).

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