Is PMS2 p.Leu323= (c.969T>A) pathogenic?

PMS2 p.Leu323= (c.969T>A) is classified Likely benign in PMS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-28). No allele count reported in gnomAD v4.1 (AN 1,585,272); Associated with Hereditary nonpolyposis colorectal neoplasms.

What condition is associated with PMS2 p.Leu323= (c.969T>A)?

PMS2 p.Leu323= (c.969T>A) is associated with Hereditary nonpolyposis colorectal neoplasms (ClinVar).

How common is PMS2 p.Leu323= (c.969T>A) in the general population?

PMS2 p.Leu323= (c.969T>A) is no allele count reported in gnomAD v4.1 (AN 1,585,272) (gnomAD).

PMS2 p.Leu323=

c.969T>A · rs1583344922 · VCV1560082

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,585,272)

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 1.3	phastCons 1
Overall
CADD	5.514	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,585,272). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PMS2
Protein: p.Leu323=
Coding: c.969T>A
MANE Select: NM_000535
dbSNP: rs1583344922
Type: single nucleotide variant
Location: chr7:5991992 (GRCh38)
Gene constraint: LOEUF 0.898 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.37 · 9 PDB
Residue 323: a β-strand

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

Similar variants

PMS2 p.Leu323Val Uncertain significance ★★ ⚠ same residue
PMS2 p.Leu323Arg Uncertain significance ★ ⚠ same residue
PMS2 p.Leu323Phe Uncertain significance ★ ⚠ same residue
PMS2 c.1145-2A>G Likely pathogenic ★★ same condition
PMS2 c.164-1G>A Pathogenic/Likely pathogenic ★★ same condition
PMS2 c.164-1G>C Pathogenic/Likely pathogenic ★★ same condition
PMS2 c.2006+1G>A Likely pathogenic ★★ same condition
PMS2 c.2007-2A>C 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-leu323 (accessed [today's date]).

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