Is MAT1A p.Val41= (c.123G>T) pathogenic?

MAT1A p.Val41= (c.123G>T) is classified Likely benign in MAT1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). Very rare (popmax 0.00667%, amr); Associated with methionine adenosyltransferase deficiency.

What condition is associated with MAT1A p.Val41= (c.123G>T)?

MAT1A p.Val41= (c.123G>T) is associated with methionine adenosyltransferase deficiency (ClinVar).

How common is MAT1A p.Val41= (c.123G>T) in the general population?

MAT1A p.Val41= (c.123G>T) is very rare (popmax 0.00667%, amr) (gnomAD).

MAT1A p.Val41=

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

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

c.123G>T · VCV4751218

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Conditions

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 0.19	GERP -2.9, phastCons 0.94
Overall
CADD	7.749	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/60,006 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00031% 5/1,614,072 alleles · very rare exomes 3/1,461,780 · genomes 2/152,292 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,002
South Asian	0.0011%	91,082

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.Val41=
Coding: c.123G>T
MANE Select: NM_000429
Type: single nucleotide variant
Location: chr10:80285558 (GRCh38)
Gene constraint: LOEUF 0.653 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 96.77 · 4 PDB
Residue 41: 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.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-val41 (accessed [today's date]).

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