MPDZ p.Ala221=
c.663C>T · rs35476999 · VCV211520
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.01%, amr)
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 2.3 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 10.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.01%
Admixed American · 6/59,846 alleles
Filtering AF
0.00429%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00296%
Overall
0.00205%
33/1,612,914 alleles · ultra-rare
exomes 32/1,460,822 · genomes 1/152,092 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.01% | 9,974 |
| European (non-Finnish) | 0.00229% | 43,679 |
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
- MPDZ
- Protein
- p.Ala221=
- Coding
- c.663C>T
- MANE Select
- NM_001378778
- dbSNP
- rs35476999
- Type
- single nucleotide variant
- Location
- chr9:13222317 (GRCh38)
- Structure
- AlphaFold pLDDT 72.11 · 3 PDB
- Residue 221
- the 'interaction with mageb18' region
Similar variants
- MPDZ c.1087-1G>A Pathogenic/Likely pathogenic ★★ same type
- MPDZ c.1474+2T>C Likely pathogenic ★★ same type
- MPDZ c.3359+1G>A Likely pathogenic ★★ same type
- MPDZ c.3360-2A>G Pathogenic/Likely pathogenic ★★ same type
- MPDZ c.4003+1G>A Pathogenic/Likely pathogenic ★★ same type
- MPDZ p.Arg1034Ter Pathogenic/Likely pathogenic ★★ same type
- MPDZ p.Arg1071Ter Pathogenic ★★ same type
- MPDZ p.Arg1170Ter 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/mpdz-p-ala221 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown