Is MAT2A p.Val230= (c.690T>C) pathogenic?

MAT2A p.Val230= (c.690T>C) is classified Likely benign in MAT2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-06). Very rare (popmax 0.00525%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with MAT2A p.Val230= (c.690T>C)?

MAT2A p.Val230= (c.690T>C) is associated with Cardiovascular phenotype, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is MAT2A p.Val230= (c.690T>C) in the general population?

MAT2A p.Val230= (c.690T>C) is very rare (popmax 0.00525%, nfe) (gnomAD).

MAT2A p.Val230=

c.690T>C · rs1478991122 · VCV1756121

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00525%, nfe)

Conditions

Cardiovascular phenotype

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 0.072	GERP -3.2, phastCons 0.97
Overall
CADD	9.063	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00525% European (non-Finnish) · 62/1,180,052 alleles

Filtering AF 0.00418% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00403% 65/1,614,098 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00525%	19,033
African / African-American	0.004%	24,979

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.Val230=
Coding: c.690T>C
MANE Select: NM_005911
dbSNP: rs1478991122
Type: single nucleotide variant
Location: chr2:85542295 (GRCh38)
Gene constraint: LOEUF 0.158 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 96.08 · 59 PDB
Residue 230: a turn

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 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-val230 (accessed [today's date]).

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