Is MSH3 p.Ser119Phe (c.356C>T) pathogenic?

MSH3 p.Ser119Phe (c.356C>T) is classified Benign/Likely benign in MSH3 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0974); Low-frequency (popmax 1.07%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with MSH3 p.Ser119Phe (c.356C>T)?

MSH3 p.Ser119Phe (c.356C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MSH3 p.Ser119Phe (c.356C>T) in the general population?

MSH3 p.Ser119Phe (c.356C>T) is low-frequency (popmax 1.07%, eas) (gnomAD).

What do computational predictors say about MSH3 p.Ser119Phe (c.356C>T)?

AlphaMissense predicts likely benign (score 0.0974) — an in-silico prediction, not a clinical call.

MSH3 p.Ser119Phe

c.356C>T · rs144607594 · VCV788096

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0974 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.07%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0974	likely benign
REVEL	0.206	benign-leaning
SaProt	LLR -8.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.86	GERP -1, phastCons 0.001
Regional constraint	o/e 1.08	unconstrained · MANE · 221 kb · p 0.0024 · regional, not allelic
Overall
CADD	19.69	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.07% East Asian · 482/44,874 alleles

Filtering AF 0.995% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.964%

Overall 0.0359% 579/1,614,132 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.07%	93
South Asian	0.0648%	1,544
Remaining individualsnot grpmax-eligible	0.0512%	1,953
Admixed American	0.00167%	60,022
European (non-Finnish)	0.000424%	235,999

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.Ser119Phe
Coding: c.356C>T
MANE Select: NM_002439
dbSNP: rs144607594
Type: single nucleotide variant
Location: chr5:80656529 (GRCh38)
Gene constraint: LOEUF 1.027 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.48 · 25 PDB
Residue 119: the 'disordered' region; the 'interaction with exo1' region

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

Similar variants

MSH3 p.Ser119Cys Likely benign ★ same residue
MSH3 c.1341-2A>C Likely pathogenic ★★ same condition
MSH3 c.1341-2A>G Likely pathogenic ★★ same condition
MSH3 c.1568+1G>C Likely pathogenic ★★ same condition
MSH3 c.1653+1G>A Likely pathogenic ★★ same condition
MSH3 c.1764-1G>A Pathogenic/Likely pathogenic ★★ same condition
MSH3 c.1764-2A>C Pathogenic/Likely pathogenic ★★ same condition
MSH3 c.1764-2A>G Pathogenic/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/msh3-p-ser119phe (accessed [today's date]).

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