MAP3K15 p.Ser503=
c.1509G>A · rs56125741 · VCV3043053
Benign
No assertion criteria
Classification
Benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 3.57%, eas)
Conditions
1
MAP3K15-related disorder
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 -1.8 | GERP -4.8 |
| Overall | ||
| CADD | 0.129 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.57%
East Asian · 1,182/33,072 alleles
Filtering AF
3.4%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.34%
Overall
0.151%
1,773/1,177,046 alleles · low-frequency
exomes 1,548/1,065,409 · genomes 225/111,637 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 3.57% | 28 |
| Ashkenazi Jewishnot grpmax-eligible | 0.98% | 102 |
| Remaining individualsnot grpmax-eligible | 0.286% | 349 |
| South Asian | 0.187% | 535 |
| Middle Eastern | 0.0231% | 4,323 |
| European (non-Finnish) | 0.0154% | 6,497 |
| African / African-American | 0.0106% | 9,470 |
| Admixed American | 0.00709% | 14,104 |
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.Ser503=
- Coding
- c.1509G>A
- MANE Select
- NM_001001671
- dbSNP
- rs56125741
- Type
- single nucleotide variant
- Location
- chrX:19415188 (GRCh38)
- Structure
- AlphaFold pLDDT 75.41 · 1 PDB
Disease context
MAP3K15-related disorder
Similar variants
- MAP3K15 p.Ser503Leu Uncertain significance ★ ⚠ same residue
- MAP3K15 p.Ile295Ser Uncertain significance ★★ ⚠ same condition
- MAP3K15 p.Leu154Phe Uncertain significance ★★ ⚠ same condition
- MAP3K15 p.Thr1229Arg Uncertain significance ★★ ⚠ same condition
- MAP3K15 p.Gln541Ter Uncertain significance same condition
- MAP3K15 c.1440-1G>T Likely benign same condition
- MAP3K15 c.719+9C>T Benign same condition
- MAP3K15 p.Ala192Thr Benign same condition
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-ser503 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown