Is MSH6 p.Arg62= (c.186C>A) pathogenic?

MSH6 p.Arg62= (c.186C>A) is classified Benign in MSH6 (ClinVar, Expert panel, 24 submitters; last evaluated 2013-09-05). Common (popmax 19%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with Lynch syndrome.

What condition is associated with MSH6 p.Arg62= (c.186C>A)?

MSH6 p.Arg62= (c.186C>A) is associated with Lynch syndrome, Lynch syndrome 5, hereditary neoplastic syndrome (ClinVar).

How is Lynch syndrome inherited?

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

MSH6 p.Arg62=

Q: How common is MSH6 p.Arg62= (c.186C>A) in the general population?

MSH6 p.Arg62= (c.186C>A) is common (popmax 19%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.186C>A · rs1042820 · VCV36584

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 24 submitters

gnomAD v4.1

Common

common (popmax 19%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

Lynch syndrome

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 -1.8	GERP -0.24
Overall
CADD	5.721	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 19% European (non-Finnish) · 214,809/1,131,530 alleles

Filtering AF 18.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.9%

Overall 16.6% 250,169/1,511,208 alleles · common exomes 231,000/1,359,046 · genomes 19,169/152,162 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	19%	5
Ashkenazi Jewishnot grpmax-eligible	16.5%	6
Middle Eastern	16.4%	6
Amishnot grpmax-eligible	16.2%	6
Remaining individualsnot grpmax-eligible	15.3%	7
Finnishnot grpmax-eligible	12.1%	8
Admixed American	10.7%	9
South Asian	7.61%	13
African / African-American	4.94%	20
East Asian	0.0486%	2,056

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.Arg62=
Coding: c.186C>A
MANE Select: NM_000179
dbSNP: rs1042820
Type: single nucleotide variant
Location: chr2:47783419 (GRCh38)
Gene constraint: LOEUF 0.841 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.93 · 8 PDB
Residue 62: the 'disordered' region

Full MSH6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: Lynch syndrome 5 hereditary neoplastic syndrome

For Lynch syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

MSH6 p.Arg62Cys Uncertain significance ★★ ⚠ same residue
MSH6 p.Arg62His Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH6 p.Arg62Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH6 p.Arg62Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH6 p.Arg62fs Pathogenic/Likely pathogenic ★★ same residue
MSH6 p.Arg62Ser Conflicting classifications of pathogenicity ★ same residue
MSH6 p.Arg62Gly Uncertain significance ★ ⚠ same residue
MSH6 c.3172+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-arg62 (accessed [today's date]).

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