Is MAT2A p.Gln112= (c.336A>G) pathogenic?

MAT2A p.Gln112= (c.336A>G) is classified Likely benign in MAT2A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-27). Ultra-rare (popmax 0.0111%, eas); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with MAT2A p.Gln112= (c.336A>G)?

MAT2A p.Gln112= (c.336A>G) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is MAT2A p.Gln112= (c.336A>G) in the general population?

MAT2A p.Gln112= (c.336A>G) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

MAT2A p.Gln112=

Q: How is Familial thoracic aortic aneurysm and aortic dissection inherited?

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

c.336A>G · rs746976689 · VCV1563376

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Conditions

familial thoracic aortic aneurysm and aortic dissection

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	GERP -4.3
Overall
CADD	4.966	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,900 alleles

Filtering AF 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00161% 26/1,613,718 alleles · ultra-rare exomes 22/1,461,474 · genomes 4/152,244 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,980
African / African-American	0.004%	24,975
South Asian	0.0033%	30,324
Remaining individualsnot grpmax-eligible	0.0016%	62,462
European (non-Finnish)	0.00119%	84,285

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.Gln112=
Coding: c.336A>G
MANE Select: NM_005911
dbSNP: rs746976689
Type: single nucleotide variant
Location: chr2:85541676 (GRCh38)
Gene constraint: LOEUF 0.158 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 96.08 · 59 PDB
Residue 112: an α-helix

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

Disease context

familial thoracic aortic aneurysm and aortic dissection — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial thoracic aortic aneurysm and aortic dissection (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

MAT2A c.292+4T>C Uncertain significance ★★ same condition
MAT2A c.549+3A>G Uncertain significance ★★ same condition
MAT2A c.952-3T>C Uncertain significance ★★ same condition
MAT2A p.Ala11Val Uncertain significance ★★ ⚠ same condition
MAT2A p.Arg177Cys Uncertain significance ★★ ⚠ same condition
MAT2A p.Arg312Gly Uncertain significance ★★ ⚠ same condition
MAT2A p.Arg343Gly Uncertain significance ★★ ⚠ same condition
MAT2A p.Arg356Cys 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-gln112 (accessed [today's date]).

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