Is MAT2A p.Arg264= (c.792C>G) pathogenic?

MAT2A p.Arg264= (c.792C>G) is classified Benign/Likely benign in MAT2A (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 68.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with MAT2A p.Arg264= (c.792C>G)?

MAT2A p.Arg264= (c.792C>G) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

MAT2A p.Arg264=

Q: How common is MAT2A p.Arg264= (c.792C>G) in the general population?

MAT2A p.Arg264= (c.792C>G) is common (popmax 68.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.792C>G · rs1078004 · VCV381190

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 68.6%, afr) — too common for a highly-penetrant pathogenic allele

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 1.8	GERP -1.1, phastCons 1
Overall
CADD	10.55	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 68.6% African / African-American · 51,391/74,892 alleles

Filtering AF 68.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 67.9%

Overall 46.4% 748,646/1,612,940 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	68.6%	1
Remaining individualsnot grpmax-eligible	47.2%	2
European (non-Finnish)	46.6%	2
Amishnot grpmax-eligible	45.9%	2
Finnishnot grpmax-eligible	45%	2
Middle Eastern	44%	2
Ashkenazi Jewishnot grpmax-eligible	40.1%	2
South Asian	39.3%	3
East Asian	38.1%	3
Admixed American	36.2%	3

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.Arg264=
Coding: c.792C>G
MANE Select: NM_005911
dbSNP: rs1078004
Type: single nucleotide variant
Location: chr2:85542588 (GRCh38)
Gene constraint: LOEUF 0.158 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 96.08 · 59 PDB
Residue 264: a binding site

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-arg264 (accessed [today's date]).

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