MAPKBP1 p.Pro1235=
c.3705G>A · rs777689645 · VCV1901108
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00769%, 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 0.017 | GERP -4.7 |
| Overall | ||
| CADD | 5.883 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00769%
South Asian · 7/91,086 alleles
Filtering AF
0.00359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00279%
Overall
0.0039%
63/1,614,168 alleles · very rare
exomes 56/1,461,870 · genomes 7/152,298 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00769% | 13,012 |
| African / African-American | 0.00533% | 18,761 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,836 |
| European (non-Finnish) | 0.00407% | 24,584 |
| East Asian | 0.00223% | 44,880 |
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.Pro1235=
- Coding
- c.3705G>A
- MANE Select
- NM_014994
- dbSNP
- rs777689645
- Type
- single nucleotide variant
- Location
- chr15:41823553 (GRCh38)
- Gene constraint
- LOEUF 0.484 · pLI 0.84 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 62.82
- Residue 1235
- the 'disordered' region
Similar variants
- MAPKBP1 p.Pro1235Leu Benign ★ 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
- MAPKBP1 p.Arg1314Trp 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-pro1235 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown