Is MSH3 p.Asp45= (c.135C>T) pathogenic?

MSH3 p.Asp45= (c.135C>T) is classified Likely benign in MSH3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-06). Very rare (popmax 0.00111%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with MSH3 p.Asp45= (c.135C>T)?

MSH3 p.Asp45= (c.135C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MSH3 p.Asp45= (c.135C>T) in the general population?

MSH3 p.Asp45= (c.135C>T) is very rare (popmax 0.00111%, sas) (gnomAD).

MSH3 p.Asp45=

c.135C>T · rs972547684 · VCV766453

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00111%, sas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.57	GERP -2.3
Overall
CADD	3.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00111% South Asian · 1/90,250 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000345% 5/1,450,190 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00111%	90,250
European (non-Finnish)	0.000341%	293,637

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: MSH3
Protein: p.Asp45=
Coding: c.135C>T
MANE Select: NM_000791 · reported on NM_002439
dbSNP: rs972547684
Type: single nucleotide variant
Location: chr5:80654862 (GRCh38)

Full MSH3 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

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/msh3-p-asp45 (accessed [today's date]).

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