Is PMS2 p.Ser329= (c.987A>G) pathogenic?

PMS2 p.Ser329= (c.987A>G) is classified Likely benign in PMS2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-02-10). Very rare (popmax 0.000184%, nfe); Associated with Hereditary nonpolyposis colorectal neoplasms.

How common is PMS2 p.Ser329= (c.987A>G) in the general population?

PMS2 p.Ser329= (c.987A>G) is very rare (popmax 0.000184%, nfe) (gnomAD).

PMS2 p.Ser329=

Q: What condition is associated with PMS2 p.Ser329= (c.987A>G)?

PMS2 p.Ser329= (c.987A>G) is associated with Hereditary nonpolyposis colorectal neoplasms, hereditary neoplastic syndrome (ClinVar).

c.987A>G · rs1783788450 · VCV942654

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000184%, nfe)

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 -1.5
Overall
CADD	6.958	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000184% European (non-Finnish) · 2/1,085,540 alleles

Filtering AF 3.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.2e-05%

Overall 0.000147% 2/1,358,176 alleles · very rare

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.Ser329=
Coding: c.987A>G
MANE Select: NM_000535
dbSNP: rs1783788450
Type: single nucleotide variant
Location: chr7:5991974 (GRCh38)
Gene constraint: LOEUF 0.898 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.37 · 9 PDB
Residue 329: an α-helix

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.Ser329Leu Uncertain significance ★★ ⚠ same residue
PMS2 p.Ser329Ter Pathogenic ★ same residue
PMS2 p.Ser329Thr Uncertain significance ★ ⚠ same residue
PMS2 p.Ser329Pro Uncertain significance ★ ⚠ 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

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-ser329 (accessed [today's date]).

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