Is MAT1A p.Val290= (c.870A>G) pathogenic?

MAT1A p.Val290= (c.870A>G) is classified Benign in MAT1A (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-03). Common (popmax 94.9%, eas) — too common for a highly-penetrant pathogenic allele; Associated with methionine adenosyltransferase deficiency.

What condition is associated with MAT1A p.Val290= (c.870A>G)?

MAT1A p.Val290= (c.870A>G) is associated with methionine adenosyltransferase deficiency (ClinVar).

MAT1A p.Val290=

Q: How common is MAT1A p.Val290= (c.870A>G) in the general population?

MAT1A p.Val290= (c.870A>G) is common (popmax 94.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Methionine adenosyltransferase I/III deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.870A>G · rs10788546 · VCV256106

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 94.9%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

methionine adenosyltransferase deficiency

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
Constraint at this position
Conservation	phyloP 1.1	GERP -0.17, phastCons 1
Overall
CADD	7.358	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 94.9% East Asian · 42,150/44,394 alleles

Filtering AF 94.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 93.9%

Overall 67.6% 1,082,398/1,602,276 alleles · common exomes 970,252/1,450,152 · genomes 112,146/152,124 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	94.9%	1
African / African-American	89.5%	1
South Asian	82.5%	1
Admixed American	78.4%	1
Middle Eastern	76.9%	1
Remaining individualsnot grpmax-eligible	70.2%	1
Ashkenazi Jewishnot grpmax-eligible	68.9%	1
Finnishnot grpmax-eligible	67.2%	1
European (non-Finnish)	63.3%	2
Amishnot grpmax-eligible	55.4%	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.Val290=
Coding: c.870A>G
MANE Select: NM_000429
dbSNP: rs10788546
Type: single nucleotide variant
Location: chr10:80275098 (GRCh38)
Gene constraint: LOEUF 0.653 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 96.77 · 4 PDB
Residue 290: an α-helix

Full MAT1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

methionine adenosyltransferase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Methionine adenosyltransferase I/III deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

MAT1A p.Val290Ile Uncertain significance ★ ⚠ same residue
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

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-val290 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown