Is MAT2A p.Cys149Ser (c.445T>A) pathogenic?

MAT2A p.Cys149Ser (c.445T>A) is classified Uncertain significance in MAT2A (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-01). AlphaMissense: ambiguous (0.502); Absent from gnomAD v4.1; Associated with Isolated thoracic aortic aneurysm.

What condition is associated with MAT2A p.Cys149Ser (c.445T>A)?

MAT2A p.Cys149Ser (c.445T>A) is associated with Isolated thoracic aortic aneurysm (ClinVar).

How common is MAT2A p.Cys149Ser (c.445T>A) in the general population?

MAT2A p.Cys149Ser (c.445T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAT2A p.Cys149Ser (c.445T>A)?

AlphaMissense predicts ambiguous (score 0.502) — an in-silico prediction, not a clinical call.

MAT2A p.Cys149Ser

c.445T>A · rs1691484259 · VCV982327

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.502 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Isolated thoracic aortic aneurysm

Computational evidence

Protein change
AlphaMissense	0.502	ambiguous
REVEL	0.546	indeterminate
SaProt	LLR -10.35	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 1,072 bp · p 2.4e-16 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAT2A
Protein: p.Cys149Ser
Coding: c.445T>A
MANE Select: NM_005911
dbSNP: rs1691484259
Type: single nucleotide variant
Location: chr2:85541868 (GRCh38)
Gene constraint: LOEUF 0.158 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 96.08 · 59 PDB

Full MAT2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Isolated thoracic aortic aneurysm

Similar variants

MAT2A p.Glu211Lys Uncertain significance ★ ⚠ same condition
MAT2A p.Ser180Cys Uncertain significance ★ ⚠ same condition
MAT2A c.292+4T>C Uncertain significance ★★ same type
MAT2A c.549+3A>G Uncertain significance ★★ same type
MAT2A c.952-3T>C Uncertain significance ★★ same type
MAT2A p.Ala11Val Uncertain significance ★★ ⚠ same type
MAT2A p.Arg177Cys Uncertain significance ★★ ⚠ same type
MAT2A p.Arg312Gly Uncertain significance ★★ ⚠ same type

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-cys149ser (accessed [today's date]).

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