Is PMS2 p.Gln237= (c.711A>G) pathogenic?

PMS2 p.Gln237= (c.711A>G) is classified Conflicting classifications of pathogenicity in PMS2 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2025-11-10). Very rare (popmax 0.00379%, nfe); Associated with Lynch syndrome.

What condition is associated with PMS2 p.Gln237= (c.711A>G)?

PMS2 p.Gln237= (c.711A>G) is associated with Lynch syndrome, Lynch syndrome 4, hereditary neoplastic syndrome (ClinVar).

How common is PMS2 p.Gln237= (c.711A>G) in the general population?

PMS2 p.Gln237= (c.711A>G) is very rare (popmax 0.00379%, nfe) (gnomAD).

How is Lynch syndrome inherited?

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

PMS2 p.Gln237=

c.711A>G · rs368608818 · VCV411068

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00379%, nfe)

Conditions

Lynch syndrome

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 -2.8
Overall
CADD	6.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00379% European (non-Finnish) · 43/1,134,640 alleles

Filtering AF 0.00285% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00254%

Overall 0.00285% 44/1,546,386 alleles · very rare exomes 44/1,418,272 · genomes 0/128,114 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00379%	26,387
Remaining individualsnot grpmax-eligible	0.00165%	60,596

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.Gln237=
Coding: c.711A>G
MANE Select: NM_000535
dbSNP: rs368608818
Type: single nucleotide variant
Location: chr7:5997418 (GRCh38)
Gene constraint: LOEUF 0.898 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.37 · 9 PDB
Residue 237: an α-helix

Full PMS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Lynch syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Lynch syndrome 4 hereditary neoplastic syndrome

For Lynch syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

PMS2 p.Gln237Ter Pathogenic/Likely pathogenic ★★ same residue
PMS2 p.Gln237Arg Uncertain significance ★★ ⚠ same residue
PMS2 p.Gln237Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
PMS2 p.Gln237fs Pathogenic ★ same residue
PMS2 p.Gln237Glu 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

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-gln237 (accessed [today's date]).

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