Is EHHADH p.Gln581= (c.1743A>G) pathogenic?

EHHADH p.Gln581= (c.1743A>G) is classified Likely benign in EHHADH (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-05-26). Ultra-rare (popmax 0.0223%, eas); Associated with EHHADH-related disorder.

What condition is associated with EHHADH p.Gln581= (c.1743A>G)?

EHHADH p.Gln581= (c.1743A>G) is associated with EHHADH-related disorder (ClinVar).

How common is EHHADH p.Gln581= (c.1743A>G) in the general population?

EHHADH p.Gln581= (c.1743A>G) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

EHHADH p.Gln581=

c.1743A>G · VCV3356949

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Conditions

EHHADH-related disorder

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 -2.3	GERP -3.9
Overall
CADD	2.285	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0223% East Asian · 10/44,902 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00916%

Overall 0.000743% 12/1,614,098 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,490
European (non-Finnish)	0.000169%	590,030

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: EHHADH
Protein: p.Gln581=
Coding: c.1743A>G
MANE Select: NM_001966
Type: single nucleotide variant
Location: chr3:185192655 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.07

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

Disease context

EHHADH-related disorder

Similar variants

EHHADH p.Gln581Arg Uncertain significance ★ ⚠ same residue
EHHADH p.Pro694Leu Uncertain significance ★★ ⚠ same condition
EHHADH p.Glu3Lys Likely pathogenic ★ ⚠ same condition
EHHADH p.Ala550Thr Uncertain significance ★ ⚠ same condition
EHHADH p.His432Tyr Uncertain significance ★ ⚠ same condition
EHHADH p.Pro225Ala Conflicting classifications of pathogenicity ★ ⚠ same condition
EHHADH p.Asp161His Uncertain significance ⚠ same condition
EHHADH p.Asp170Asn 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/ehhadh-p-gln581 (accessed [today's date]).

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