Is MSH6 p.Pro85= (c.255C>A) pathogenic?

MSH6 p.Pro85= (c.255C>A) is classified Benign/Likely benign in MSH6 (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-02-03). Very rare (popmax 0.00926%, nfe); Associated with Hereditary nonpolyposis colorectal neoplasms.

How common is MSH6 p.Pro85= (c.255C>A) in the general population?

MSH6 p.Pro85= (c.255C>A) is very rare (popmax 0.00926%, nfe) (gnomAD).

MSH6 p.Pro85=

Q: What condition is associated with MSH6 p.Pro85= (c.255C>A)?

MSH6 p.Pro85= (c.255C>A) is associated with Hereditary nonpolyposis colorectal neoplasms, Lynch syndrome, Lynch syndrome 5 (ClinVar).

c.255C>A · rs587779242 · VCV89288

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00926%, nfe)

Conditions

Hereditary nonpolyposis colorectal neoplasms

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -4.7	GERP -3.3
Overall
CADD	6.39	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00926% European (non-Finnish) · 101/1,090,546 alleles

Filtering AF 0.00775% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.00736% 105/1,427,282 alleles · very rare exomes 94/1,275,246 · genomes 11/152,036 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00926%	10,797
Admixed American	0.00922%	10,843
Remaining individualsnot grpmax-eligible	0.00183%	54,650

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.Pro85=
Coding: c.255C>A
MANE Select: NM_000179
dbSNP: rs587779242
Type: single nucleotide variant
Location: chr2:47783488 (GRCh38)

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 Lynch syndrome 5 hereditary neoplastic syndrome

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-pro85 (accessed [today's date]).

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