Is PMS2 p.Phe242= (c.726T>C) pathogenic?

PMS2 p.Phe242= (c.726T>C) is classified Likely benign in PMS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-12-03). Very rare (popmax 0.00111%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with PMS2 p.Phe242= (c.726T>C)?

PMS2 p.Phe242= (c.726T>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is PMS2 p.Phe242= (c.726T>C) in the general population?

PMS2 p.Phe242= (c.726T>C) is very rare (popmax 0.00111%, sas) (gnomAD).

PMS2 p.Phe242=

c.726T>C · rs1346863182 · VCV922791

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00111%, sas)

Conditions

hereditary neoplastic 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 0.23	phastCons 0.001
Overall
CADD	8.684	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00111% South Asian · 1/90,004 alleles

Overall 6.26e-05% 1/1,597,874 alleles · very rare exomes 1/1,448,794 · genomes 0/149,080 · joint denominator

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.Phe242=
Coding: c.726T>C
MANE Select: NM_000535
dbSNP: rs1346863182
Type: single nucleotide variant
Location: chr7:5997403 (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

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

Similar variants

PMS2 p.Phe242Leu Uncertain significance ★★ ⚠ same residue
PMS2 p.Phe242fs Pathogenic ★★ same residue
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
PMS2 c.2174+1G>A Pathogenic ★★★ same condition
PMS2 c.705+1G>T Likely pathogenic ★★★ same condition
PMS2 c.989-2A>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-phe242 (accessed [today's date]).

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