Is MSH6 p.Asp439fs (c.1315_1318del) pathogenic?

MSH6 p.Asp439fs (c.13151318del) is classified Pathogenic in MSH6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-11). Absent from gnomAD; Associated with Hereditary nonpolyposis colorectal neoplasms.

What condition is associated with MSH6 p.Asp439fs (c.1315_1318del)?

MSH6 p.Asp439fs (c.1315_1318del) is associated with Hereditary nonpolyposis colorectal neoplasms, Lynch syndrome 5 (ClinVar).

How common is MSH6 p.Asp439fs (c.1315_1318del) in the general population?

MSH6 p.Asp439fs (c.1315_1318del) is absent from gnomAD (gnomAD).

MSH6 p.Asp439fs

c.1315_1318del · rs2104335533 · VCV1460121

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Hereditary nonpolyposis colorectal neoplasms

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.51	GERP -0.83, phastCons 0.028

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: MSH6
Protein: p.Asp439fs
Coding: c.1315_1318del
MANE Select: NM_000179
dbSNP: rs2104335533
Type: Deletion
Location: chr2:47799295 (GRCh38)
Gene constraint: LOEUF 0.841 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.93 · 8 PDB
Residue 439: an α-helix

Full MSH6 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

Also linked: Lynch syndrome 5

Similar variants

MSH6 p.Asp439Gly Pathogenic/Likely pathogenic ★★ same residue
MSH6 p.Asp439= Benign/Likely benign ★★ same residue
MSH6 c.3173-1_3173del Pathogenic ★★★ same condition
MSH6 c.3379_3438+5del Pathogenic ★★★ same condition
MSH6 p.Arg1242del Likely pathogenic ★★★ same condition
MSH6 p.Asn1039_Phe1040insTer Pathogenic ★★★ same condition
MSH6 p.Asp380fs Pathogenic ★★★ same condition
MSH6 p.Glu995fs 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/msh6-p-asp439fs (accessed [today's date]).

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