Is MAT2A p.Ala302= (c.906A>G) pathogenic?

MAT2A p.Ala302= (c.906A>G) is classified Likely benign in MAT2A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-30). Very rare (popmax 0.00133%, afr); Associated with Cardiovascular phenotype.

What condition is associated with MAT2A p.Ala302= (c.906A>G)?

MAT2A p.Ala302= (c.906A>G) is associated with Cardiovascular phenotype (ClinVar).

How common is MAT2A p.Ala302= (c.906A>G) in the general population?

MAT2A p.Ala302= (c.906A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

MAT2A p.Ala302=

c.906A>G · VCV3543597

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Cardiovascular phenotype

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 5.3	GERP 1.1, phastCons 1
Overall
CADD	14.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,012 alleles

Overall 6.2e-05% 1/1,613,562 alleles · very rare exomes 1/1,461,286 · genomes 0/152,276 · joint denominator

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: MAT2A
Protein: p.Ala302=
Coding: c.906A>G
MANE Select: NM_005911
Type: single nucleotide variant
Location: chr2:85542702 (GRCh38)
Gene constraint: LOEUF 0.158 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 96.08 · 59 PDB
Residue 302: an α-helix

Full MAT2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAT2A c.549+3A>G Uncertain significance ★★ same condition
MAT2A p.Ala11Val Uncertain significance ★★ ⚠ same condition
MAT2A p.Asn6His Uncertain significance ★★ ⚠ same condition
MAT2A p.Asn6Ile Uncertain significance ★★ ⚠ same condition
MAT2A p.Gln4Arg Uncertain significance ★★ ⚠ same condition
MAT2A p.Ile154Val Uncertain significance ★★ ⚠ same condition
MAT2A p.Ile241Val Uncertain significance ★★ ⚠ same condition
MAT2A p.Leu19Phe Uncertain significance ★★ ⚠ 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/mat2a-p-ala302 (accessed [today's date]).

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