Is MAT2A p.Val87Phe (c.259G>T) pathogenic?

MAT2A p.Val87Phe (c.259G>T) is classified Uncertain significance in MAT2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-19). AlphaMissense: likely pathogenic (0.7627); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with MAT2A p.Val87Phe (c.259G>T)?

MAT2A p.Val87Phe (c.259G>T) is associated with Cardiovascular phenotype (ClinVar).

How common is MAT2A p.Val87Phe (c.259G>T) in the general population?

MAT2A p.Val87Phe (c.259G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAT2A p.Val87Phe (c.259G>T)?

AlphaMissense predicts likely pathogenic (score 0.7627) — an in-silico prediction, not a clinical call.

MAT2A p.Val87Phe

c.259G>T · VCV4104415

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7627 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.7627	likely pathogenic
REVEL	0.778	moderately pathogenic-leaning
SaProt	LLR -13.92	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.1, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 1,072 bp · p 2.4e-16 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Val87Phe
Coding: c.259G>T
MANE Select: NM_005911
Type: single nucleotide variant
Location: chr2:85541344 (GRCh38)
Gene constraint: LOEUF 0.158 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 96.08 · 59 PDB
Residue 87: 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 p.Val87Leu Uncertain significance ★ ⚠ same residue
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

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-val87phe (accessed [today's date]).

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