Is MSH6 p.Phe10= (c.30C>T) pathogenic?

MSH6 p.Phe10= (c.30C>T) is classified Benign/Likely benign in MSH6 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-04-16). Very rare (popmax 8.48e-05%, nfe); Associated with Hereditary nonpolyposis colorectal neoplasms.

What condition is associated with MSH6 p.Phe10= (c.30C>T)?

MSH6 p.Phe10= (c.30C>T) is associated with Hereditary nonpolyposis colorectal neoplasms, Lynch syndrome 5, hereditary neoplastic syndrome (ClinVar).

How common is MSH6 p.Phe10= (c.30C>T) in the general population?

MSH6 p.Phe10= (c.30C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

MSH6 p.Phe10=

c.30C>T · rs786201869 · VCV185320

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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 3.7	GERP 1.1, phastCons 1
Overall
CADD	15.53	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,586 alleles

Overall 0.000124% 2/1,612,182 alleles · very rare exomes 2/1,459,856 · genomes 0/152,326 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,444
European (non-Finnish)grpmax	8.48e-05%	1,179,586

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe10=
Coding: c.30C>T
MANE Select: NM_000179
dbSNP: rs786201869
Type: single nucleotide variant
Location: chr2:47783263 (GRCh38)
Gene constraint: LOEUF 0.841 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.93 · 8 PDB
Residue 10: the 'disordered' region

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 hereditary neoplastic syndrome

Similar variants

MSH6 p.Phe10Cys Uncertain significance ★★ ⚠ same residue
MSH6 p.Phe10Ile Uncertain significance ★★ ⚠ same residue
MSH6 p.Phe10Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH6 p.Phe10Val Uncertain significance ★ ⚠ same residue
MSH6 p.Phe10fs Pathogenic ★ same residue
MSH6 p.Phe10Tyr 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-phe10 (accessed [today's date]).

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