MAP4K2 p.Ser227=
c.681G>A · VCV3870307
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0231%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Pangolin | Δ0.21 | loss · gain 0.01 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP -6.3 | GERP -3.9 |
| Overall | ||
| CADD | 2.776 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0231%
South Asian · 21/90,792 alleles
Filtering AF
0.0154%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.013%
Overall
0.0023%
37/1,611,580 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0231% | 4,323 |
| African / African-American | 0.00134% | 74,896 |
| European (non-Finnish) | 0.00127% | 78,603 |
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
- MAP4K2
- Protein
- p.Ser227=
- Coding
- c.681G>A
- MANE Select
- NM_004579
- Type
- single nucleotide variant
- Location
- chr11:64800808 (GRCh38)
- Gene constraint
- LOEUF 0.867 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.32
- Residue 227
- the protein kinase domain
Similar variants
- MAP4K2 p.Ala120Ser Benign ★★ same type
- MAP4K2 p.Asn606= Benign ★★ same type
- MAP4K2 p.Ala183Asp Uncertain significance ★ ⚠ same type
- MAP4K2 p.Ala184Ser Uncertain significance ★ ⚠ same type
- MAP4K2 p.Ala405Thr Uncertain significance ★ ⚠ same type
- MAP4K2 p.Ala487Thr Uncertain significance ★ ⚠ same type
- MAP4K2 p.Ala790Asp Uncertain significance ★ ⚠ same type
- MAP4K2 p.Ala806Val 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/map4k2-p-ser227 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown