Is ETFA p.Val270del (c.806TAG[1]) pathogenic?

ETFA p.Val270del (c.806TAG[1]) is classified Conflicting classifications of pathogenicity in ETFA (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2025-07-28). Very rare (popmax 0.00562%, nfe); Associated with Glutaric acidemia type 2A.

What condition is associated with ETFA p.Val270del (c.806TAG[1])?

ETFA p.Val270del (c.806TAG[1]) is associated with Glutaric acidemia type 2A, multiple acyl-CoA dehydrogenase deficiency, glutaric acidemia IIa (ClinVar).

How common is ETFA p.Val270del (c.806TAG[1]) in the general population?

ETFA p.Val270del (c.806TAG[1]) is very rare (popmax 0.00562%, nfe) (gnomAD).

ETFA p.Val270del

c.806TAG[1] · rs779140971 · VCV1209001

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00562%, nfe)

Conditions

Glutaric acidemia type 2A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Overall
CADD	19.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00562% European (non-Finnish) · 66/1,174,472 alleles

Filtering AF 0.00453% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00413%

Overall 0.00411% 66/1,605,790 alleles · very rare

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.Val270del
Coding: c.806TAG[1]
MANE Select: NM_000126
dbSNP: rs779140971
Type: Microsatellite
Location: chr15:76274417 (GRCh38)
Gene constraint: LOEUF 1.166 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.00 · 4 PDB
Residue 270: the 'domain ii' region

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 glutaric acidemia IIa

Similar variants

ETFA p.Val270= Likely benign ★ same residue
ETFA p.His107fs Pathogenic/Likely pathogenic ★★ same condition
ETFA p.Ile108fs Pathogenic/Likely pathogenic ★★ same condition
ETFA c.37_39+1del Likely pathogenic ★ same condition
ETFA p.Glu198fs Pathogenic ★ same condition
MADD p.Ser1178fs Likely pathogenic ★ same condition
MADD p.Glu270Gln Uncertain significance ★ ⚠ same residue
ETFA c.817-12_817-11del Likely benign ★ 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-val270del (accessed [today's date]).

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