Is HADH p.Phe200= (c.600T>C) pathogenic?

HADH p.Phe200= (c.600T>C) is classified Likely benign in HADH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-14). Very rare (popmax 0.00446%, eas); Associated with 3-hydroxyacyl-CoA dehydrogenase deficiency.

What condition is associated with HADH p.Phe200= (c.600T>C)?

HADH p.Phe200= (c.600T>C) is associated with 3-hydroxyacyl-CoA dehydrogenase deficiency (ClinVar).

How common is HADH p.Phe200= (c.600T>C) in the general population?

HADH p.Phe200= (c.600T>C) is very rare (popmax 0.00446%, eas) (gnomAD).

HADH p.Phe200=

c.600T>C · rs766283075 · VCV2883026

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

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 -0.49	GERP -5.1, phastCons 0.039
Overall
CADD	6.268	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,862 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000434% 7/1,611,654 alleles · very rare exomes 7/1,459,322 · genomes 0/152,332 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,431
South Asian	0.0022%	45,511
Remaining individualsnot grpmax-eligible	0.0016%	62,410
European (non-Finnish)	0.00017%	588,869

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.Phe200=
Coding: c.600T>C
MANE Select: NM_005327
dbSNP: rs766283075
Type: single nucleotide variant
Location: chr4:108023527 (GRCh38)
Gene constraint: LOEUF 1.09 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.90 · 12 PDB
Residue 200: 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-phe200 (accessed [today's date]).

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