MTPAP p.Ala220=
c.660G>A · rs556574328 · VCV1957339
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0121%, sas)
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 -20 | GERP -3.3 |
| Overall | ||
| CADD | 0.009 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0121%
South Asian · 11/91,034 alleles
Filtering AF
0.00677%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00522%
Overall
0.00136%
22/1,613,346 alleles · ultra-rare
exomes 19/1,461,086 · genomes 3/152,260 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0121% | 8,276 |
| East Asian | 0.00668% | 14,963 |
| Admixed American | 0.00167% | 60,018 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,440 |
| African / African-American | 0.00133% | 74,994 |
| European (non-Finnish) | 0.000424% | 235,985 |
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
- MTPAP
- Protein
- p.Ala220=
- Coding
- c.660G>A
- MANE Select
- NM_018109
- dbSNP
- rs556574328
- Type
- single nucleotide variant
- Location
- chr10:30336923 (GRCh38)
- Gene constraint
- LOEUF 0.641 · pLI 0.03 (gnomAD)
- Structure
- AlphaFold pLDDT 83.16 · 1 PDB
- Residue 220
- a turn
Similar variants
- MTPAP p.Ala220Ser Uncertain significance ★ ⚠ same residue
- MTPAP p.Ala220Thr Uncertain significance ★ ⚠ same residue
- MTPAP p.Ala220Val Uncertain significance ★ ⚠ same residue
- MTPAP p.Asn478Asp Pathogenic ★★ ⚠ same type
- MTPAP p.Ala141Thr Uncertain significance ★★ ⚠ same type
- MTPAP p.Ala219Thr Uncertain significance ★★ ⚠ same type
- MTPAP p.Arg160Trp Uncertain significance ★★ ⚠ same type
- MTPAP p.Arg171Cys 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/mtpap-p-ala220 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown