MN1 p.Ala290=
c.870C>T · VCV4947314
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00331%, nfe)
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 0.26 | GERP -2.5, phastCons 0.96 |
| Overall | ||
| CADD | 7.709 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00331%
European (non-Finnish) · 38/1,148,330 alleles
Filtering AF
0.00246%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00215%
Overall
0.00258%
40/1,551,918 alleles · very rare
exomes 35/1,399,842 · genomes 5/152,076 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00331% | 30,219 |
| Remaining individualsnot grpmax-eligible | 0.00166% | 60,102 |
| African / African-American | 0.00137% | 73,246 |
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
- MN1
- Protein
- p.Ala290=
- Coding
- c.870C>T
- MANE Select
- NM_002430
- Type
- single nucleotide variant
- Location
- chr22:27799674 (GRCh38)
- Gene constraint
- LOEUF 0.482 · pLI 0.99 (gnomAD)
- Structure
- AlphaFold pLDDT 42.47
- Residue 290
- the 'disordered' region
Similar variants
- MN1 p.Ala290Ser Uncertain significance ★ ⚠ same residue
- MN1 p.Gln1273Ter Pathogenic ★★ same type
- MN1 p.Lys455Ter Likely pathogenic ★★ same type
- MN1 p.Trp1248Ter Pathogenic/Likely pathogenic ★★ same type
- MN1 p.Ala38Asp Uncertain significance ★★ ⚠ same type
- MN1 p.Gly1092Arg Uncertain significance ★★ ⚠ same type
- MN1 p.Gly120Val Uncertain significance ★★ ⚠ same type
- MN1 p.Gly161Arg Uncertain significance ★★ ⚠ same type
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/mn1-p-ala290 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown