Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Common
common (popmax 95%, eas) — too common for a highly-penetrant pathogenic allele
Conditions
1
methionine adenosyltransferase deficiency
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.3 | GERP -1.1, phastCons 1 |
| Overall | ||
| CADD | 5.485 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
95%
East Asian · 42,598/44,834 alleles
Filtering AF
94.3%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 93.9%
Overall
70.6%
1,139,937/1,613,670 alleles · common
exomes 1,022,897/1,461,780 · genomes 117,040/151,890 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 95% | 1 |
| African / African-American | 93.9% | 1 |
| South Asian | 83.6% | 1 |
| Middle Eastern | 81.9% | 1 |
| Admixed American | 80.6% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 75.4% | 1 |
| Remaining individualsnot grpmax-eligible | 73.6% | 1 |
| Finnishnot grpmax-eligible | 69.7% | 1 |
| European (non-Finnish) | 66.5% | 2 |
| Amishnot grpmax-eligible | 60.9% | 2 |
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
- MAT1A
- Protein
- p.Ala142=
- Coding
- c.426T>C
- MANE Select
- NM_000429
- dbSNP
- rs1143694
- Type
- single nucleotide variant
- Location
- chr10:80280296 (GRCh38)
- Gene constraint
- LOEUF 0.653 · pLI 0.06 (gnomAD)
- Structure
- AlphaFold pLDDT 96.77 · 4 PDB
- Residue 142
- a β-strand
Disease context
methionine adenosyltransferase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Methionine adenosyltransferase I/III deficiency (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy
Similar variants
- MAT1A p.Ala259Val Pathogenic ★★ same condition
- MAT1A p.Arg199Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
- MAT1A p.Arg199His Pathogenic ★★ ⚠ same condition
- MAT1A p.Arg264Cys Pathogenic ★★ same condition
- MAT1A p.Arg264His Pathogenic ★★ same condition
- MAT1A p.Arg292Cys Pathogenic/Likely pathogenic ★★ same condition
- MAT1A p.Arg299Cys Pathogenic/Likely pathogenic ★★ same condition
- MAT1A p.Asp258Tyr Pathogenic/Likely pathogenic ★★ same condition
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/mat1a-p-ala142 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown