Is PMS2 p.Asp97= (c.291C>T) pathogenic?

PMS2 p.Asp97= (c.291C>T) is classified Likely benign in PMS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-19). Very rare (popmax 0.00017%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with PMS2 p.Asp97= (c.291C>T)?

PMS2 p.Asp97= (c.291C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is PMS2 p.Asp97= (c.291C>T) in the general population?

PMS2 p.Asp97= (c.291C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

PMS2 p.Asp97=

c.291C>T · VCV4824561

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

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 6.5	phastCons 1
Overall
CADD	9.885	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,234 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000125% 2/1,603,546 alleles · very rare exomes 2/1,451,290 · genomes 0/152,256 · 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.Asp97=
Coding: c.291C>T
MANE Select: NM_000535
Type: single nucleotide variant
Location: chr7:6003752 (GRCh38)
Gene constraint: LOEUF 0.898 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.37 · 9 PDB
Residue 97: an α-helix

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.Asp97Asn Uncertain significance ★★ ⚠ same residue
PMS2 p.Asp97Glu Uncertain significance ★★ ⚠ same residue
PMS2 p.Asp97Gly Uncertain significance ★★ ⚠ same residue
PMS2 p.Asp97His Uncertain significance ★★ ⚠ same residue
PMS2 p.Asp97Val Uncertain significance ★ ⚠ same residue
PMS2 p.Asp97Tyr Uncertain significance ★★ ⚠ same residue
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-asp97 (accessed [today's date]).

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