MTPAP p.Phe453=
c.1359C>T · rs768612271 · VCV761087
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0243%, sas)
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 4.4 | GERP -0.94, phastCons 1 |
| Overall | ||
| CADD | 12.31 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0243%
South Asian · 22/90,552 alleles
Filtering AF
0.0164%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0138%
Overall
0.00361%
58/1,605,158 alleles · ultra-rare
exomes 52/1,453,180 · genomes 6/151,978 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0243% | 4,116 |
| Admixed American | 0.0134% | 7,461 |
| African / African-American | 0.00401% | 24,908 |
| Remaining individualsnot grpmax-eligible | 0.00322% | 31,070 |
| European (non-Finnish) | 0.00196% | 51,037 |
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.Phe453=
- Coding
- c.1359C>T
- MANE Select
- NM_018109
- dbSNP
- rs768612271
- Type
- single nucleotide variant
- Location
- chr10:30315990 (GRCh38)
- Gene constraint
- LOEUF 0.641 · pLI 0.03 (gnomAD)
- Structure
- AlphaFold pLDDT 83.16 · 1 PDB
- Residue 453
- the pap-associated domain
Similar variants
- 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
- MTPAP p.Arg461Gln Uncertain significance ★★ ⚠ same type
- MTPAP p.Arg76Gln Uncertain significance ★★ ⚠ same type
- MTPAP p.Asn129Ser 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-phe453 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown