MSH6 p.Val282=
c.846G>C · rs573638836 · VCV386786
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0472%, sas)
Conditions
2
hereditary neoplastic 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 -0.72 | GERP -3.8 |
| Overall | ||
| CADD | 0.715 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0472%
South Asian · 43/91,072 alleles
Filtering AF
0.036%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0321%
Overall
0.00285%
46/1,614,160 alleles · ultra-rare
exomes 42/1,461,878 · genomes 4/152,282 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0472% | 2,118 |
| Admixed American | 0.00167% | 60,016 |
| European (non-Finnish) | 0.000169% | 590,012 |
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.Val282=
- Coding
- c.846G>C
- MANE Select
- NM_000179
- dbSNP
- rs573638836
- Type
- single nucleotide variant
- Location
- chr2:47798829 (GRCh38)
- Gene constraint
- LOEUF 0.841 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.93 · 8 PDB
- Residue 282
- the 'disordered' region
Similar variants
- MSH6 p.Val282Ala Uncertain significance ★★ ⚠ same residue
- MSH6 p.Val282Gly Uncertain significance ★★ ⚠ same residue
- MSH6 p.Val282Leu Uncertain significance ★★ ⚠ same residue
- MSH6 p.Val282Met Uncertain significance ★★ ⚠ same residue
- MSH6 p.Val282fs Pathogenic ★★ same residue
- MSH6 c.3172+1G>T Likely pathogenic ★★★ same condition
- MSH6 c.3438+1G>A Likely pathogenic ★★★ same condition
- MSH6 c.3439-1G>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-val282 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown