Is MSH6 p.Pro386= (c.1158T>C) pathogenic?

MSH6 p.Pro386= (c.1158T>C) is classified Likely benign in MSH6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-29). Absent from gnomAD v4.1; Associated with Hereditary nonpolyposis colorectal neoplasms.

What condition is associated with MSH6 p.Pro386= (c.1158T>C)?

MSH6 p.Pro386= (c.1158T>C) is associated with Hereditary nonpolyposis colorectal neoplasms (ClinVar).

How common is MSH6 p.Pro386= (c.1158T>C) in the general population?

MSH6 p.Pro386= (c.1158T>C) is absent from gnomAD v4.1 (gnomAD).

MSH6 p.Pro386=

c.1158T>C · rs1553412550 · VCV1159396

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Hereditary nonpolyposis colorectal neoplasms

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -9.9	GERP -4.1
Overall
CADD	0.996	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MSH6
Protein: p.Pro386=
Coding: c.1158T>C
MANE Select: NM_000179
dbSNP: rs1553412550
Type: single nucleotide variant
Location: chr2:47799141 (GRCh38)
Gene constraint: LOEUF 0.841 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.93 · 8 PDB

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

Similar variants

MSH6 p.Pro386Ser Uncertain significance ★★ ⚠ same residue
MSH6 p.Pro386Ala Uncertain significance ★ ⚠ same residue
MSH6 p.Pro386Leu Uncertain significance ★★ ⚠ same residue
MSH6 p.Pro386Arg Uncertain significance ★ ⚠ same residue
MSH6 c.3173-3C>G Pathogenic/Likely pathogenic ★★ same condition
MSH6 c.3557-1G>A Likely pathogenic ★★ same condition
MSH6 c.3557-1G>C Pathogenic/Likely pathogenic ★★ same condition
MSH6 c.3557-1G>T 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/msh6-p-pro386 (accessed [today's date]).

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