Is MSH6 p.Ser830= (c.2490T>C) pathogenic?

MSH6 p.Ser830= (c.2490T>C) is classified Benign/Likely benign in MSH6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-31). Absent from gnomAD v4.1; Associated with Hereditary nonpolyposis colorectal neoplasms.

What condition is associated with MSH6 p.Ser830= (c.2490T>C)?

MSH6 p.Ser830= (c.2490T>C) is associated with Hereditary nonpolyposis colorectal neoplasms, Lynch syndrome 5 (ClinVar).

How common is MSH6 p.Ser830= (c.2490T>C) in the general population?

MSH6 p.Ser830= (c.2490T>C) is absent from gnomAD v4.1 (gnomAD).

MSH6 p.Ser830=

c.2490T>C · rs2104409329 · VCV1556136

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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 1.2	GERP 1.3, phastCons 1
Overall
CADD	6.141	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.Ser830=
Coding: c.2490T>C
MANE Select: NM_000179
dbSNP: rs2104409329
Type: single nucleotide variant
Location: chr2:47800473 (GRCh38)
Gene constraint: LOEUF 0.841 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.93 · 8 PDB
Residue 830: a modified residue (phosphoserine)

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.Ser830Ala Uncertain significance ★★ ⚠ same residue
MSH6 p.Ser830Cys Uncertain significance ★★ ⚠ same residue
MSH6 p.Ser830Tyr Uncertain significance ★ ⚠ same residue
MSH6 p.Ser830Phe Uncertain significance ★★ ⚠ same residue
MSH6 p.Ser830Pro Uncertain significance ★ ⚠ same residue
MSH6 c.3172+1G>T Likely pathogenic ★★★ same condition
MSH6 c.3438+1G>A Likely pathogenic ★★★ same condition
MSH6 c.3439-1G>T 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-ser830 (accessed [today's date]).

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