Is MAT2A p.Ser341Arg (c.1023T>A) pathogenic?

MAT2A p.Ser341Arg (c.1023T>A) is classified Uncertain significance in MAT2A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-27). AlphaMissense: ambiguous (0.5354); Very rare (popmax 0.0011%, sas); Associated with Cardiovascular phenotype.

What condition is associated with MAT2A p.Ser341Arg (c.1023T>A)?

MAT2A p.Ser341Arg (c.1023T>A) is associated with Cardiovascular phenotype (ClinVar).

How common is MAT2A p.Ser341Arg (c.1023T>A) in the general population?

MAT2A p.Ser341Arg (c.1023T>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about MAT2A p.Ser341Arg (c.1023T>A)?

AlphaMissense predicts ambiguous (score 0.5354) — an in-silico prediction, not a clinical call.

MAT2A p.Ser341Arg

c.1023T>A · VCV3543611

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5354 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.5354	ambiguous
REVEL	0.803	moderately pathogenic-leaning
SaProt	LLR -10.59	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 2.2, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 1,053 bp · p 2.3e-09 · regional, not allelic
Overall
CADD	23.8	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

Grpmax group 0.0011% South Asian · 1/91,048 alleles

Overall 0.000124% 2/1,613,462 alleles · very rare exomes 2/1,461,436 · genomes 0/152,026 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,048
European (non-Finnish)	8.48e-05%	1,179,871

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.Ser341Arg
Coding: c.1023T>A
MANE Select: NM_005911
Type: single nucleotide variant
Location: chr2:85542972 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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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-ser341arg (accessed [today's date]).

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