Is MAT2A p.Ser96= (c.288C>T) pathogenic?

MAT2A p.Ser96= (c.288C>T) is classified Likely benign in MAT2A (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-21). Very rare (popmax 0.0011%, sas); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with MAT2A p.Ser96= (c.288C>T)?

MAT2A p.Ser96= (c.288C>T) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is MAT2A p.Ser96= (c.288C>T) in the general population?

MAT2A p.Ser96= (c.288C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

MAT2A p.Ser96=

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.288C>T · rs1691471820 · VCV1095720

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 -0.38	GERP -2.4, phastCons 0.077
Overall
CADD	12.53	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,590 alleles

Overall 6.2e-05% 1/1,611,634 alleles · very rare exomes 1/1,459,360 · genomes 0/152,274 · 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.Ser96=
Coding: c.288C>T
MANE Select: NM_005911
dbSNP: rs1691471820
Type: single nucleotide variant
Location: chr2:85541373 (GRCh38)
Gene constraint: LOEUF 0.158 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 96.08 · 59 PDB
Residue 96: 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 p.Ser96Ala Uncertain significance ★ ⚠ same residue
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

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-ser96 (accessed [today's date]).

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