MAPKBP1 p.Pro775=
c.2325G>A · rs749213495 · VCV2420660
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0483%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.28 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.74 | GERP -4, phastCons 0.83 |
| Overall | ||
| CADD | 12.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0483%
Admixed American · 29/59,996 alleles
Filtering AF
0.0345%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0299%
Overall
0.00254%
41/1,613,960 alleles · ultra-rare
exomes 39/1,461,880 · genomes 2/152,080 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0483% | 2,069 |
| African / African-American | 0.00267% | 37,433 |
| South Asian | 0.0022% | 45,539 |
| European (non-Finnish) | 0.000678% | 147,504 |
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
- MAPKBP1
- Protein
- p.Pro775=
- Coding
- c.2325G>A
- MANE Select
- NM_014994
- dbSNP
- rs749213495
- Type
- single nucleotide variant
- Location
- chr15:41819279 (GRCh38)
- Gene constraint
- LOEUF 0.484 · pLI 0.84 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 62.82
- Residue 775
- the 'disordered' region
Similar variants
- MAPKBP1 p.Pro775Ala Uncertain significance ★ ⚠ same residue
- MAPKBP1 p.Pro775Leu Uncertain significance ★ ⚠ same residue
- MAPKBP1 c.1711+5G>A Uncertain significance ★★ same type
- MAPKBP1 p.Ala1126Pro Uncertain significance ★★ ⚠ same type
- MAPKBP1 p.Ala1407Thr Uncertain significance ★★ ⚠ same type
- MAPKBP1 p.Ala1427Ser Uncertain significance ★★ ⚠ same type
- MAPKBP1 p.Ala146Thr Uncertain significance ★★ ⚠ same type
- MAPKBP1 p.Arg1102Cys 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/mapkbp1-p-pro775 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown