Is MAT2A p.Tyr271= (c.813T>C) pathogenic?

MAT2A p.Tyr271= (c.813T>C) is classified Benign/Likely benign in MAT2A (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Low-frequency (popmax 1.85%, eas); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with MAT2A p.Tyr271= (c.813T>C)?

MAT2A p.Tyr271= (c.813T>C) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is MAT2A p.Tyr271= (c.813T>C) in the general population?

MAT2A p.Tyr271= (c.813T>C) is low-frequency (popmax 1.85%, eas) (gnomAD).

MAT2A p.Tyr271=

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.813T>C · rs149459768 · VCV477587

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.85%, 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 -20	GERP -4.1
Overall
CADD	0.007	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.85% East Asian · 832/44,874 alleles

Filtering AF 1.75% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.71%

Overall 0.0761% 1,229/1,614,084 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.85%	54
Remaining individualsnot grpmax-eligible	0.142%	702
South Asian	0.119%	843
Admixed American	0.0667%	1,500
Middle Eastern	0.0495%	2,021
African / African-American	0.0267%	3,752
European (non-Finnish)	0.0114%	8,806
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,799
Finnishnot grpmax-eligible	0.00156%	64,044

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.Tyr271=
Coding: c.813T>C
MANE Select: NM_005911
dbSNP: rs149459768
Type: single nucleotide variant
Location: chr2:85542609 (GRCh38)
Gene constraint: LOEUF 0.158 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 96.08 · 59 PDB
Residue 271: a turn

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-tyr271 (accessed [today's date]).

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