Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 29.1%, sas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +252 | deep intronic (+252 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.14 | GERP -1 |
| Non-coding constraint | Z 3.80 | 1 kb window · o/e 0.75 · regional · uncalibrated |
| Overall | ||
| CADD | 1.548 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
29.1%
South Asian · 1,407/4,830 alleles
Filtering AF
27.9%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 27.4%
Overall
18.7%
28,495/152,254 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 29.1% | 3 |
| Finnishnot grpmax-eligible | 28.7% | 3 |
| East Asian | 27.4% | 4 |
| European (non-Finnish) | 22.8% | 4 |
| Admixed American | 21.5% | 5 |
| Ashkenazi Jewishnot grpmax-eligible | 20.5% | 5 |
| Amishnot grpmax-eligible | 19.5% | 5 |
| Remaining individualsnot grpmax-eligible | 17.7% | 6 |
| Middle Eastern | 15.6% | 6 |
| African / African-American | 6.15% | 16 |
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
- MAP2K2
- Coding
- c.919+252C>T
- MANE Select
- NM_030662
- dbSNP
- rs1979013
- Type
- single nucleotide variant
- Location
- chr19:4098949 (GRCh38)
- Gene constraint
- LOEUF 0.858 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.54 · 3 PDB
Similar variants
- MAP2K2 p.Glu207Lys Likely pathogenic ★★★ same type
- MAP2K2 p.Phe57Cys Pathogenic ★★★ same type
- MAP2K2 p.Phe57Val Pathogenic ★★★ same type
- MAP2K2 p.Pro128Gln Pathogenic ★★★ same type
- MAP2K2 p.Tyr134Cys Likely pathogenic ★★★ same type
- MAP2K2 p.Tyr134His Pathogenic ★★★ same type
- MAP2K2 p.Arg231His Uncertain significance ★★★ ⚠ same type
- MAP2K2 p.Arg231Leu 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/map2k2-c-919-plus-252c-t (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown