Is EHHADH p.Ser328= (c.984G>A) pathogenic?

EHHADH p.Ser328= (c.984G>A) is classified Likely benign in EHHADH (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-05-19). Very rare (popmax 0.00667%, amr); Associated with EHHADH-related disorder.

What condition is associated with EHHADH p.Ser328= (c.984G>A)?

EHHADH p.Ser328= (c.984G>A) is associated with EHHADH-related disorder (ClinVar).

How common is EHHADH p.Ser328= (c.984G>A) in the general population?

EHHADH p.Ser328= (c.984G>A) is very rare (popmax 0.00667%, amr) (gnomAD).

EHHADH p.Ser328=

c.984G>A · rs372621913 · VCV3036943

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Conditions

EHHADH-related disorder

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 -0.71	GERP -3.3
Overall
CADD	6.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/59,976 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00322% 52/1,613,954 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,994
Finnishnot grpmax-eligible	0.00625%	16,004
South Asian	0.00329%	30,363
Remaining individualsnot grpmax-eligible	0.0032%	31,243
European (non-Finnish)	0.00314%	31,892
African / African-American	0.00267%	37,437

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: EHHADH
Protein: p.Ser328=
Coding: c.984G>A
MANE Select: NM_001966
dbSNP: rs372621913
Type: single nucleotide variant
Location: chr3:185193414 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.07
Residue 328: the '3-hydroxyacyl-coa dehydrogenase' region

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

Disease context

EHHADH-related disorder

Similar variants

EHHADH p.Ser328Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
EHHADH p.Pro694Leu Uncertain significance ★★ ⚠ same condition
EHHADH p.Glu3Lys Likely pathogenic ★ ⚠ same condition
EHHADH p.Ala550Thr Uncertain significance ★ ⚠ same condition
EHHADH p.His432Tyr Uncertain significance ★ ⚠ same condition
EHHADH p.Pro225Ala Conflicting classifications of pathogenicity ★ ⚠ same condition
EHHADH p.Asp161His Uncertain significance ⚠ same condition
EHHADH p.Asp170Asn 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/ehhadh-p-ser328 (accessed [today's date]).

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