MAP3K1 p.Ser989del
c.2959TCT[2] · VCV3910462
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.011%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 6 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 12.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.011%
African / African-American · 8/72,952 alleles
Filtering AF
0.0054%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00389%
Overall
0.00323%
52/1,611,900 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.011% | 9,119 |
| Admixed American | 0.00334% | 29,957 |
| European (non-Finnish) | 0.00322% | 31,052 |
| Finnishnot grpmax-eligible | 0.00312% | 32,014 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| South Asian | 0.0011% | 91,090 |
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
- MAP3K1
- Protein
- p.Ser989del
- Coding
- c.2959TCT[2]
- MANE Select
- NM_005921
- Type
- Microsatellite
- Location
- chr5:56882157 (GRCh38)
- Gene constraint
- LOEUF 0.355 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.80 · 1 PDB
Similar variants
- MAP3K1 p.Thr949del Benign ★★ same type
- MAP3K1 p.Thr948_Thr949dup Uncertain significance ★ same type
- MAP3K1 c.1687-17GT[2] Likely benign ★ same type
- MAP3K1 p.Thr946_Thr949del Likely benign ★ same type
- MAP3K1 p.Thr948_Thr949del Likely benign ★ same type
- MAP3K1 p.Thr949_Glu950insThr Likely 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/map3k1-p-ser989del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown