MME p.Ala463=
c.1389C>T · rs140315924 · VCV1597032
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0469%, eas)
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 -8 | GERP -4.6 |
| Overall | ||
| CADD | 0.524 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0469%
East Asian · 21/44,744 alleles
Filtering AF
0.0314%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0263%
Overall
0.00459%
74/1,611,546 alleles · ultra-rare
exomes 58/1,460,240 · genomes 16/151,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0469% | 2,131 |
| African / African-American | 0.0161% | 6,217 |
| Admixed American | 0.0117% | 8,549 |
| Remaining individualsnot grpmax-eligible | 0.00641% | 15,599 |
| South Asian | 0.00549% | 18,198 |
| European (non-Finnish) | 0.00212% | 47,148 |
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
- MME
- Protein
- p.Ala463=
- Coding
- c.1389C>T
- MANE Select
- NM_007289
- dbSNP
- rs140315924
- Type
- single nucleotide variant
- Location
- chr3:155144430 (GRCh38)
- Gene constraint
- LOEUF 0.931 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.25 · 16 PDB
- Residue 463
- the peptidase m13 domain; an α-helix
Similar variants
- MME c.1497+1G>A Likely pathogenic ★★ same type
- MME c.1497+1G>C Likely pathogenic ★★ same type
- MME c.160+2T>C Likely pathogenic ★★ same type
- MME c.1601+2T>C Likely pathogenic ★★ same type
- MME c.1781-2A>G Pathogenic/Likely pathogenic ★★ same type
- MME c.439+1G>A Likely pathogenic ★★ same type
- MME c.440-2A>C Pathogenic/Likely pathogenic ★★ same type
- MME c.536-1G>A Pathogenic/Likely pathogenic ★★ 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/mme-p-ala463 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown