MAP3K15 p.Pro219=
c.657G>C · rs200022856 · VCV2660132
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.115%, mid)
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 -9.9 | GERP -4.1 |
| Overall | ||
| CADD | 0.026 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.115%
Middle Eastern · 5/4,350 alleles
Filtering AF
0.0452%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0293%
Overall
0.00651%
78/1,197,774 alleles · rare
exomes 73/1,086,656 · genomes 5/111,118 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.115% | 870 |
| South Asian | 0.0441% | 2,268 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0182% | 5,505 |
| Remaining individualsnot grpmax-eligible | 0.00842% | 11,874 |
| Admixed American | 0.00659% | 15,180 |
| European (non-Finnish) | 0.00414% | 24,181 |
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
- MAP3K15
- Protein
- p.Pro219=
- Coding
- c.657G>C
- MANE Select
- NM_001001671
- dbSNP
- rs200022856
- Type
- single nucleotide variant
- Location
- chrX:19464275 (GRCh38)
- Structure
- AlphaFold pLDDT 75.41 · 1 PDB
Similar variants
- MAP3K15 p.Pro219Leu Uncertain significance ★ ⚠ same residue
- MAP3K15 p.Ala859Thr Uncertain significance ★★ ⚠ same type
- MAP3K15 p.Ile295Ser Uncertain significance ★★ ⚠ same type
- MAP3K15 p.Leu154Phe Uncertain significance ★★ ⚠ same type
- MAP3K15 p.Thr1229Arg Uncertain significance ★★ ⚠ same type
- MAP3K15 p.Ser199Asn Benign ★★ same type
- MAP3K15 p.Val455Ile Likely benign ★★ same type
- PDHA1 c.*1013C>A Benign ★★ 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/map3k15-p-pro219 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown