Is HADH p.Val265= (c.795C>T) pathogenic?

HADH p.Val265= (c.795C>T) is classified Benign/Likely benign in HADH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-06). Very rare (popmax 0.00667%, amr); Associated with 3-hydroxyacyl-CoA dehydrogenase deficiency.

What condition is associated with HADH p.Val265= (c.795C>T)?

HADH p.Val265= (c.795C>T) is associated with 3-hydroxyacyl-CoA dehydrogenase deficiency, hyperinsulinemic hypoglycemia (ClinVar).

How common is HADH p.Val265= (c.795C>T) in the general population?

HADH p.Val265= (c.795C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

HADH p.Val265=

c.795C>T · rs143416676 · VCV744099

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

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 -3.5	GERP -5.4
Overall
CADD	5.842	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/59,954 alleles

Filtering AF 0.00321% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00284%

Overall 0.00365% 58/1,589,932 alleles · very rare exomes 54/1,437,922 · genomes 4/152,010 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,989
East Asian	0.00447%	22,389
European (non-Finnish)	0.00414%	24,129
African / African-American	0.00269%	37,208
Remaining individualsnot grpmax-eligible	0.00162%	61,646
Finnishnot grpmax-eligible	0.00156%	63,994

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.Val265=
Coding: c.795C>T
MANE Select: NM_005327
dbSNP: rs143416676
Type: single nucleotide variant
Location: chr4:108033261 (GRCh38)
Gene constraint: LOEUF 1.09 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.90 · 12 PDB
Residue 265: 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

Also linked: hyperinsulinemic hypoglycemia

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-val265 (accessed [today's date]).

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