Is PMS2 p.Thr511Val (c.1531_1532inv) pathogenic?

PMS2 p.Thr511Val (c.15311532inv) is classified Uncertain significance in PMS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-03-05). Associated with hereditary neoplastic syndrome.

What condition is associated with PMS2 p.Thr511Val (c.1531_1532inv)?

PMS2 p.Thr511Val (c.1531_1532inv) is associated with hereditary neoplastic syndrome (ClinVar).

PMS2 p.Thr511Val

c.1531_1532inv · VCV630535

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

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 · substitutions only
Constraint at this position
Conservation	phyloP -3.7
Regional constraint	o/e 1.09	unconstrained · MANE · 22 kb · p 0.015 · regional, not allelic
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Variant & gene context

Gene: PMS2
Protein: p.Thr511Val
Coding: c.1531_1532inv
MANE Select: NM_000535
Type: Inversion
Location: chr7:5987233 (GRCh38)
Gene constraint: LOEUF 0.898 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.37 · 9 PDB
Residue 511: the 'disordered' region; a UniProt-annotated variant site (in lynch4; benign; normal dna mismatch repair activity); a UniProt-annotated variant site (normal dna mismatch repair activity); a UniProt-annotated variant site (in)

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.Thr511Ala Benign ★★★ same residue
PMS2 p.Thr511Met Benign ★★★ same residue
PMS2 p.Thr511fs Pathogenic ★★ same residue
PMS2 p.Thr511Ser Uncertain significance ★★ ⚠ same residue
PMS2 p.Thr511= Benign/Likely benign ★★ same residue
PMS2 p.Ser260Trp Uncertain significance ★★ same condition
PMS2 p.Thr558Arg Uncertain significance ★★ same condition
PMS2 c.163+2T>C 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-thr511val (accessed [today's date]).

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