Is MAT2B p.Asp151Val (c.452A>T) pathogenic?

MAT2B p.Asp151Val (c.452A>T) is classified Uncertain significance in MAT2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely pathogenic (0.8412); Absent from gnomAD v4.1.

How common is MAT2B p.Asp151Val (c.452A>T) in the general population?

MAT2B p.Asp151Val (c.452A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAT2B p.Asp151Val (c.452A>T)?

AlphaMissense predicts likely pathogenic (score 0.8412) — an in-silico prediction, not a clinical call.

MAT2B p.Asp151Val

c.452A>T · VCV4104422

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8412 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8412	likely pathogenic
REVEL	0.413	indeterminate
SaProt	LLR -11.57	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.6, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 13 kb · p 0.0009 · 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: MAT2B
Protein: p.Asp151Val
Coding: c.452A>T
MANE Select: NM_013283
Type: single nucleotide variant
Location: chr5:163513920 (GRCh38)
Gene constraint: LOEUF 0.671 · pLI 0.34 (gnomAD)
Structure: AlphaFold pLDDT 93.82 · 9 PDB

Full MAT2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAT2B p.Ala196Pro Uncertain significance ★ ⚠ same type
MAT2B p.Ala55Thr Uncertain significance ★ ⚠ same type
MAT2B p.Arg219Lys Uncertain significance ★ ⚠ same type
MAT2B p.Arg289His Uncertain significance ★ ⚠ same type
MAT2B p.Arg30Gly Uncertain significance ★ ⚠ same type
MAT2B p.Arg312Gln Uncertain significance ★ ⚠ same type
MAT2B p.Asn253Ser Uncertain significance ★ ⚠ same type
MAT2B p.Asn270Ser 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/mat2b-p-asp151val (accessed [today's date]).

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