Is MAT2A p.Arg177= (c.531C>T) pathogenic?

MAT2A p.Arg177= (c.531C>T) is classified Likely benign in MAT2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). Very rare (popmax 0.004%, afr); Associated with Cardiovascular phenotype.

What condition is associated with MAT2A p.Arg177= (c.531C>T)?

MAT2A p.Arg177= (c.531C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is MAT2A p.Arg177= (c.531C>T) in the general population?

MAT2A p.Arg177= (c.531C>T) is very rare (popmax 0.004%, afr) (gnomAD).

MAT2A p.Arg177=

c.531C>T · VCV4052030

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.85	GERP 1.1, phastCons 1
Overall
CADD	12.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,940 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,613,846 alleles · very rare exomes 2/1,461,614 · genomes 2/152,232 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,980
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Arg177=
Coding: c.531C>T
MANE Select: NM_005911
Type: single nucleotide variant
Location: chr2:85541954 (GRCh38)
Gene constraint: LOEUF 0.158 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 96.08 · 59 PDB
Residue 177: a β-strand

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.Arg177Cys 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-arg177 (accessed [today's date]).

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