MAPKBP1 p.Cys258=
c.774C>T · rs373664505 · VCV1496463
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0301%, amr)
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 -0.097 | GERP 1.5, phastCons 0.54 |
| Overall | ||
| CADD | 15.64 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0301%
Admixed American · 18/59,760 alleles
Filtering AF
0.0195%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.016%
Overall
0.00409%
66/1,612,262 alleles · ultra-rare
exomes 55/1,460,058 · genomes 11/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0301% | 3,320 |
| South Asian | 0.011% | 9,076 |
| African / African-American | 0.00935% | 10,694 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,206 |
| European (non-Finnish) | 0.00246% | 40,662 |
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.Cys258=
- Coding
- c.774C>T
- MANE Select
- NM_014994
- dbSNP
- rs373664505
- Type
- single nucleotide variant
- Location
- chr15:41813056 (GRCh38)
- Gene constraint
- LOEUF 0.484 · pLI 0.84 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 62.82
Similar variants
- 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
- MAPKBP1 p.Arg1337Ser 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-cys258 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown