MME p.Val623=
c.1869G>C · rs189182286 · VCV1551327
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0383%, amr)
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 0.94 | GERP -4, phastCons 0.96 |
| Overall | ||
| CADD | 5.64 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0383%
Admixed American · 23/59,996 alleles
Filtering AF
0.0261%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0222%
Overall
0.00149%
24/1,613,812 alleles · ultra-rare
exomes 18/1,461,544 · genomes 6/152,268 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0383% | 2,609 |
| African / African-American | 0.00133% | 75,024 |
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.Val623=
- Coding
- c.1869G>C
- MANE Select
- NM_007289
- dbSNP
- rs189182286
- Type
- single nucleotide variant
- Location
- chr3:155168580 (GRCh38)
- Gene constraint
- LOEUF 0.931 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.25 · 16 PDB
- Residue 623
- an α-helix; the peptidase m13 domain
Similar variants
- MME p.Val623Met Uncertain significance ★ ⚠ same residue
- 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
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-val623 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown