Is PMS2 p.Arg211Ter (c.631C>T) pathogenic?

PMS2 p.Arg211Ter (c.631C>T) is classified Pathogenic in PMS2 (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-01-18). Very rare (popmax 0.0011%, sas); Associated with PMS2-related disorder.

What condition is associated with PMS2 p.Arg211Ter (c.631C>T)?

PMS2 p.Arg211Ter (c.631C>T) is associated with PMS2-related disorder, gastric cancer, Lynch syndrome (ClinVar).

How common is PMS2 p.Arg211Ter (c.631C>T) in the general population?

PMS2 p.Arg211Ter (c.631C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

PMS2 p.Arg211Ter

c.631C>T · rs760228510 · VCV234508

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

PMS2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 6 of 15
Splicing
SpliceAI	Δ0.26	acceptor loss, 44 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 5.5	phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,082 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000274% 4/1,461,856 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,082
European (non-Finnish)	0.000254%	393,332

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.Arg211Ter
Coding: c.631C>T
MANE Select: NM_000535
dbSNP: rs760228510
Type: single nucleotide variant
Location: chr7:5999182 (GRCh38)
Gene constraint: LOEUF 0.898 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.37 · 9 PDB
Residue 211: a β-strand

Full PMS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PMS2-related disorder

Also linked: gastric cancer Lynch syndrome Lynch syndrome 4 hereditary neoplastic syndrome mismatch repair cancer syndrome 4

Similar variants

PMS2 p.Arg211Gly Uncertain significance ★★ ⚠ same residue
PMS2 p.Arg211Leu Uncertain significance ★★ same residue
PMS2 p.Arg211Pro Uncertain significance ★★ ⚠ same residue
PMS2 p.Arg211= Benign/Likely benign ★★ same residue
PMS2 p.Arg211Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
PMS2 p.Arg211fs Pathogenic ★★ same residue
PMS2 p.Arg211del Uncertain significance ★ same residue
PMS2 c.1144+2T>A 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-arg211ter (accessed [today's date]).

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