METAP1 p.Ala378=
c.1134A>G · rs79876289 · VCV783426
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.59%, afr)
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 | Δ0.36 | gain · loss 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP -6 | GERP -3.3 |
| Overall | ||
| CADD | 0.893 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.59%
African / African-American · 1,947/75,050 alleles
Filtering AF
2.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.46%
Overall
0.144%
2,329/1,613,796 alleles · low-frequency
exomes 1,214/1,461,464 · genomes 1,115/152,332 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.59% | 39 |
| Remaining individualsnot grpmax-eligible | 0.213% | 470 |
| Admixed American | 0.158% | 631 |
| Middle Eastern | 0.0992% | 1,008 |
| European (non-Finnish) | 0.0123% | 8,136 |
| South Asian | 0.0033% | 30,345 |
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
- METAP1
- Protein
- p.Ala378=
- Coding
- c.1134A>G
- MANE Select
- NM_015143
- dbSNP
- rs79876289
- Type
- single nucleotide variant
- Location
- chr4:99061290 (GRCh38)
- Gene constraint
- LOEUF 0.877 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.44 · 41 PDB
Similar variants
- MAP1A p.Arg2734Gln Uncertain significance ★★ same type
- MAP1A p.Gly567Ala Uncertain significance ★★ ⚠ same type
- MAP1A p.Gly482= Benign/Likely benign ★★ same type
- MAP1A p.Leu1621Val Benign ★★ same type
- MAP1A p.Ser1152= Likely benign ★★ same type
- MAP1A p.Ser1311= Benign/Likely benign ★★ same type
- MAP1A p.Ser1544= Benign ★★ same type
- MAP1A p.Ser1858Cys 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/metap1-p-ala378 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown