Is MAT2A p.Ser95Pro (c.283T>C) pathogenic?

MAT2A p.Ser95Pro (c.283T>C) is classified Uncertain significance in MAT2A (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-19). AlphaMissense: ambiguous (0.3759); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with MAT2A p.Ser95Pro (c.283T>C)?

MAT2A p.Ser95Pro (c.283T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is MAT2A p.Ser95Pro (c.283T>C) in the general population?

MAT2A p.Ser95Pro (c.283T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAT2A p.Ser95Pro (c.283T>C)?

AlphaMissense predicts ambiguous (score 0.3759) — an in-silico prediction, not a clinical call.

MAT2A p.Ser95Pro

c.283T>C · VCV4844405

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3759 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.3759	ambiguous
REVEL	0.844	moderately pathogenic-leaning
SaProt	LLR -9.45	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 1,072 bp · p 2.4e-16 · regional, not allelic
Overall
CADD	31.0	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.Ser95Pro
Coding: c.283T>C
MANE Select: NM_005911
Type: single nucleotide variant
Location: chr2:85541368 (GRCh38)
Gene constraint: LOEUF 0.158 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 96.08 · 59 PDB
Residue 95: an α-helix

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

Similar variants

MAT2A c.549+3A>G Uncertain significance ★★ same condition
MAT2A p.Ala11Val Uncertain significance ★★ ⚠ same condition
MAT2A p.Asn6His Uncertain significance ★★ ⚠ same condition
MAT2A p.Asn6Ile Uncertain significance ★★ ⚠ same condition
MAT2A p.Gln4Arg Uncertain significance ★★ ⚠ same condition
MAT2A p.Ile154Val Uncertain significance ★★ ⚠ same condition
MAT2A p.Ile241Val Uncertain significance ★★ ⚠ same condition
MAT2A p.Leu19Phe 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-ser95pro (accessed [today's date]).

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