MAP3K8 p.Ser125=
c.375C>T · rs112441933 · VCV1625978
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0987%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.033 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -8.5 | GERP -3.5 |
| Overall | ||
| CADD | 1.339 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0987%
African / African-American · 74/75,008 alleles
Filtering AF
0.0805%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0739%
Overall
0.0145%
234/1,613,684 alleles · ultra-rare
exomes 182/1,461,442 · genomes 52/152,242 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0987% | 1,014 |
| Middle Eastern | 0.066% | 1,516 |
| Remaining individualsnot grpmax-eligible | 0.0304% | 3,289 |
| Admixed American | 0.015% | 6,656 |
| European (non-Finnish) | 0.0105% | 9,515 |
| Finnishnot grpmax-eligible | 0.00469% | 21,336 |
| East Asian | 0.00223% | 44,870 |
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
- MAP3K8
- Protein
- p.Ser125=
- Coding
- c.375C>T
- MANE Select
- NM_005204
- dbSNP
- rs112441933
- Type
- single nucleotide variant
- Location
- chr10:30447820 (GRCh38)
- Gene constraint
- LOEUF 0.58 · pLI 0.73 (gnomAD)
- Structure
- AlphaFold pLDDT 74.13 · 3 PDB
- Residue 125
- a turn
Similar variants
- MAP3K8 p.Ala35Ser Uncertain significance ★★ ⚠ same type
- MAP3K8 p.Ala450Thr Uncertain significance ★★ same type
- MAP3K8 p.Arg392Gly Uncertain significance ★★ ⚠ same type
- MAP3K8 p.Arg408Ser Uncertain significance ★★ ⚠ same type
- MAP3K8 p.Asn54Asp Uncertain significance ★★ ⚠ same type
- MAP3K8 p.Gly67Asp Uncertain significance ★★ ⚠ same type
- MAP3K8 p.Ile190Val Uncertain significance ★★ ⚠ same type
- MAP3K8 p.Met277Ile 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/map3k8-p-ser125 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown