Is MAT2A p.Ile205Val (c.613A>G) pathogenic?

MAT2A p.Ile205Val (c.613A>G) is classified Likely benign in MAT2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-24). AlphaMissense: likely benign (0.124); Ultra-rare (popmax 0.0395%, sas); Associated with Cardiovascular phenotype.

What condition is associated with MAT2A p.Ile205Val (c.613A>G)?

MAT2A p.Ile205Val (c.613A>G) is associated with Cardiovascular phenotype, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is MAT2A p.Ile205Val (c.613A>G) in the general population?

MAT2A p.Ile205Val (c.613A>G) is ultra-rare (popmax 0.0395%, sas) (gnomAD).

What do computational predictors say about MAT2A p.Ile205Val (c.613A>G)?

AlphaMissense predicts likely benign (score 0.124) — an in-silico prediction, not a clinical call.

MAT2A p.Ile205Val

c.613A>G · rs141849127 · VCV1055985

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.124 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0395%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.124	likely benign
REVEL	0.266	benign-leaning
SaProt	LLR -5.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.42 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.4	GERP 2.2, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 1,072 bp · p 2.4e-16 · regional, not allelic
Overall
CADD	21.4	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 0.0395% South Asian · 36/91,086 alleles

Filtering AF 0.0293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0258%

Overall 0.00341% 55/1,614,060 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0395%	2,530
East Asian	0.00668%	14,967
Remaining individualsnot grpmax-eligible	0.0032%	31,244
European (non-Finnish)	0.00119%	84,288

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.Ile205Val
Coding: c.613A>G
MANE Select: NM_005911
dbSNP: rs141849127
Type: single nucleotide variant
Location: chr2:85542218 (GRCh38)
Gene constraint: LOEUF 0.158 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 96.08 · 59 PDB
Residue 205: 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

Also linked: familial thoracic aortic aneurysm and aortic dissection

Similar variants

MAT2A p.Ile205Thr Uncertain significance ★ ⚠ same residue
MAT2A c.292+4T>C Uncertain significance ★★ same condition
MAT2A c.549+3A>G Uncertain significance ★★ same condition
MAT2A c.952-3T>C Uncertain significance ★★ same condition
MAT2A p.Ala11Val Uncertain significance ★★ ⚠ same condition
MAT2A p.Arg177Cys Uncertain significance ★★ ⚠ same condition
MAT2A p.Arg312Gly Uncertain significance ★★ ⚠ same condition
MAT2A p.Arg343Gly 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-ile205val (accessed [today's date]).

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