Is ETFA p.Met1Val (c.1A>G) pathogenic?

ETFA p.Met1Val (c.1A>G) is classified Pathogenic in ETFA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-27). Very rare (popmax 0.00118%, sas); Associated with Glutaric acidemia type 2A.

What condition is associated with ETFA p.Met1Val (c.1A>G)?

ETFA p.Met1Val (c.1A>G) is associated with Glutaric acidemia type 2A, multiple acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ETFA p.Met1Val (c.1A>G) in the general population?

ETFA p.Met1Val (c.1A>G) is very rare (popmax 0.00118%, sas) (gnomAD).

ETFA p.Met1Val

c.1A>G · VCV3577725

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00118%, sas)

Conditions

Glutaric acidemia type 2A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.552	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 1.3, phastCons 1
Overall
CADD	20.6	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00118% South Asian · 1/85,032 alleles

Filtering AF 8.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000355% 5/1,410,290 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00118%	85,032
European (non-Finnish)	0.000346%	288,633

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: ETFA
Protein: p.Met1Val
Coding: c.1A>G
MANE Select: NM_000126
Type: single nucleotide variant
Location: chr15:76311388 (GRCh38)
Gene constraint: LOEUF 1.166 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.00 · 4 PDB

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

Disease context

Glutaric acidemia type 2A

Also linked: multiple acyl-CoA dehydrogenase deficiency

Similar variants

ETFA p.Met1Ile Pathogenic/Likely pathogenic ★★ same residue
ETFA p.Met1Thr Conflicting classifications of pathogenicity ★ same residue
ETFA p.Met1_Ala6del Conflicting classifications of pathogenicity ★ same residue
ETFA c.186+1G>A Likely pathogenic ★★ same condition
ETFA c.39+1G>A Likely pathogenic ★★ same condition
ETFA c.451+1G>A Likely pathogenic ★★ same condition
ETFA c.452-2A>G Likely pathogenic ★★ same condition
ETFA c.664+1G>A Likely pathogenic ★★ 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/etfa-p-met1val (accessed [today's date]).

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