Is MSH6 p.Asp562= (c.1686T>C) pathogenic?

MSH6 p.Asp562= (c.1686T>C) is classified Benign/Likely benign in MSH6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-27). Very rare (popmax 0.0011%, sas); Associated with Lynch syndrome 5.

What condition is associated with MSH6 p.Asp562= (c.1686T>C)?

MSH6 p.Asp562= (c.1686T>C) is associated with Lynch syndrome 5, Lynch syndrome (ClinVar).

How common is MSH6 p.Asp562= (c.1686T>C) in the general population?

MSH6 p.Asp562= (c.1686T>C) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Lynch syndrome inherited?

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

MSH6 p.Asp562=

c.1686T>C · rs2104360615 · VCV3073403

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 -0.32	GERP -4.6, phastCons 0.24
Overall
CADD	2.39	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,088 alleles

Overall 6.19e-05% 1/1,614,216 alleles · very rare exomes 1/1,461,886 · genomes 0/152,330 · joint denominator

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: MSH6
Protein: p.Asp562=
Coding: c.1686T>C
MANE Select: NM_000179
dbSNP: rs2104360615
Type: single nucleotide variant
Location: chr2:47799669 (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: Lynch syndrome

For Lynch syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

MSH6 p.Asp562Ala Uncertain significance ★ ⚠ same residue
MSH6 p.Asp562Asn Uncertain significance ★ ⚠ same residue
MSH6 p.Asp562Glu Uncertain significance ★ ⚠ same residue
MSH6 p.Asp562Gly Uncertain significance ★ ⚠ same residue
MSH6 p.Asp562His Uncertain significance ★ ⚠ same residue
MSH6 p.Asp562Tyr 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-asp562 (accessed [today's date]).

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