Is MSH6 p.Ser549= (c.1647T>G) pathogenic?

MSH6 p.Ser549= (c.1647T>G) is classified Benign/Likely benign in MSH6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-27). No allele count reported in gnomAD v4.1 (AN 1,614,170); Associated with Lynch syndrome 5.

What condition is associated with MSH6 p.Ser549= (c.1647T>G)?

MSH6 p.Ser549= (c.1647T>G) is associated with Lynch syndrome 5, hereditary neoplastic syndrome (ClinVar).

How common is MSH6 p.Ser549= (c.1647T>G) in the general population?

MSH6 p.Ser549= (c.1647T>G) is no allele count reported in gnomAD v4.1 (AN 1,614,170) (gnomAD).

How is Lynch syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

MSH6 p.Ser549=

c.1647T>G · rs2104358212 · VCV3230511

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,170)

Conditions

Lynch syndrome 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.91	GERP -1.6, phastCons 0.76
Overall
CADD	6.53	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,614,170). 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.Ser549=
Coding: c.1647T>G
MANE Select: NM_000179
dbSNP: rs2104358212
Type: single nucleotide variant
Location: chr2:47799630 (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

Lynch syndrome 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Lynch syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

MSH6 p.Ser549Phe Uncertain significance ★★ ⚠ same residue
MSH6 p.Ser549Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH6 p.Ser549Thr Uncertain significance ★ ⚠ same residue
MSH6 p.Ser549Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH6 p.Ser549fs Pathogenic ★★ same residue
MSH6 p.Ser549Pro Uncertain significance ★ ⚠ same residue
MSH6 c.3172+1G>T Likely pathogenic ★★★ same condition
MSH6 c.3438+1G>A 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-ser549 (accessed [today's date]).

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