Is HADH p.Arg6= (c.18G>A) pathogenic?

HADH p.Arg6= (c.18G>A) is classified Likely benign in HADH (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-02). Rare (popmax 0.189%, afr); Associated with 3-hydroxyacyl-CoA dehydrogenase deficiency.

What condition is associated with HADH p.Arg6= (c.18G>A)?

HADH p.Arg6= (c.18G>A) is associated with 3-hydroxyacyl-CoA dehydrogenase deficiency (ClinVar).

How common is HADH p.Arg6= (c.18G>A) in the general population?

HADH p.Arg6= (c.18G>A) is rare (popmax 0.189%, afr) (gnomAD).

HADH p.Arg6=

c.18G>A · rs146017663 · VCV2085736

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.189%, afr)

Conditions

3-hydroxyacyl-CoA dehydrogenase deficiency

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 1	GERP 0.94, phastCons 1
Overall
CADD	11.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.189% African / African-American · 142/75,032 alleles

Filtering AF 0.164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.154%

Overall 0.00924% 149/1,612,966 alleles · rare exomes 75/1,460,608 · genomes 74/152,358 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.189%	528
Admixed American	0.005%	19,997
Remaining individualsnot grpmax-eligible	0.0032%	31,236
European (non-Finnish)	0.00017%	589,831

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: HADH
Protein: p.Arg6=
Coding: c.18G>A
MANE Select: NM_005327
dbSNP: rs146017663
Type: single nucleotide variant
Location: chr4:107989950 (GRCh38)
Gene constraint: LOEUF 1.09 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.90 · 12 PDB
Residue 6: an α-helix

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

Disease context

3-hydroxyacyl-CoA dehydrogenase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

HADH c.261+1G>A Pathogenic/Likely pathogenic ★★ same condition
HADH c.262-2A>G Likely pathogenic ★★ same condition
HADH c.709+2T>C Likely pathogenic ★★ same condition
HADH p.Arg236Ter Pathogenic/Likely pathogenic ★★ same condition
HADH p.Gly34Arg Likely pathogenic ★★ same condition
HADH p.Ala239Ser Uncertain significance ★★ ⚠ same condition
HADH p.Glu235Asp Uncertain significance ★★ ⚠ same condition
HADH p.Gly34Ser 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/hadh-p-arg6 (accessed [today's date]).

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