Is HADH p.Ser196= (c.588T>G) pathogenic?

HADH p.Ser196= (c.588T>G) is classified Likely benign in HADH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-23). Absent from gnomAD v4.1; Associated with 3-hydroxyacyl-CoA dehydrogenase deficiency.

What condition is associated with HADH p.Ser196= (c.588T>G)?

HADH p.Ser196= (c.588T>G) is associated with 3-hydroxyacyl-CoA dehydrogenase deficiency (ClinVar).

How common is HADH p.Ser196= (c.588T>G) in the general population?

HADH p.Ser196= (c.588T>G) is absent from gnomAD v4.1 (gnomAD).

HADH p.Ser196=

c.588T>G · VCV3700727

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.66	GERP 0.11, phastCons 1
Overall
CADD	8.262	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: HADH
Protein: p.Ser196=
Coding: c.588T>G
MANE Select: NM_005327
Type: single nucleotide variant
Location: chr4:108023515 (GRCh38)
Gene constraint: LOEUF 1.09 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.90 · 12 PDB
Residue 196: 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-ser196 (accessed [today's date]).

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