Is HADH p.Pro291= (c.873A>G) pathogenic?

HADH p.Pro291= (c.873A>G) is classified Likely benign in HADH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-18). Very rare (popmax 8.48e-05%, nfe); Associated with 3-hydroxyacyl-CoA dehydrogenase deficiency.

What condition is associated with HADH p.Pro291= (c.873A>G)?

HADH p.Pro291= (c.873A>G) is associated with 3-hydroxyacyl-CoA dehydrogenase deficiency (ClinVar).

How common is HADH p.Pro291= (c.873A>G) in the general population?

HADH p.Pro291= (c.873A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

HADH p.Pro291=

c.873A>G · rs1736381152 · VCV2802479

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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 -3	GERP -5.4
Overall
CADD	0.143	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,716 alleles

Overall 6.2e-05% 1/1,613,764 alleles · very rare exomes 0/1,461,516 · genomes 1/152,248 · joint denominator

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.Pro291=
Coding: c.873A>G
MANE Select: NM_005327
dbSNP: rs1736381152
Type: single nucleotide variant
Location: chr4:108034285 (GRCh38)
Gene constraint: LOEUF 1.09 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.90 · 12 PDB
Residue 291: 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-pro291 (accessed [today's date]).

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