Is MAT2A p.Ile330= (c.990C>T) pathogenic?

MAT2A p.Ile330= (c.990C>T) is classified Likely benign in MAT2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-27). Very rare (popmax 0.000254%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with MAT2A p.Ile330= (c.990C>T)?

MAT2A p.Ile330= (c.990C>T) is associated with Cardiovascular phenotype, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is MAT2A p.Ile330= (c.990C>T) in the general population?

MAT2A p.Ile330= (c.990C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

MAT2A p.Ile330=

c.990C>T · rs1387934407 · VCV1546363

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.23	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 6	GERP 1.2, phastCons 1
Overall
CADD	17.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,866 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,566 alleles · very rare exomes 2/1,461,376 · genomes 1/152,190 · 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.Ile330=
Coding: c.990C>T
MANE Select: NM_005911
dbSNP: rs1387934407
Type: single nucleotide variant
Location: chr2:85542939 (GRCh38)
Gene constraint: LOEUF 0.158 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 96.08 · 59 PDB
Residue 330: a β-strand

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

Also linked: familial thoracic aortic aneurysm and aortic dissection

Similar variants

MAT2A p.Ile330Val Uncertain significance ★★ ⚠ same residue
MAT2A p.Ile330fs 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

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-ile330 (accessed [today's date]).

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