Is EHHADH p.Ala640= (c.1920T>C) pathogenic?

EHHADH p.Ala640= (c.1920T>C) is classified Likely benign in EHHADH (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-08-30). Ultra-rare (popmax 0.0493%, mid); Associated with EHHADH-related disorder.

What condition is associated with EHHADH p.Ala640= (c.1920T>C)?

EHHADH p.Ala640= (c.1920T>C) is associated with EHHADH-related disorder (ClinVar).

How common is EHHADH p.Ala640= (c.1920T>C) in the general population?

EHHADH p.Ala640= (c.1920T>C) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

EHHADH p.Ala640=

c.1920T>C · rs1166523943 · VCV3032736

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

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 -0.13	GERP -0.52
Overall
CADD	5.315	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00715%

Overall 0.00112% 18/1,614,138 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
European (non-Finnish)	0.00127%	78,670

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.Ala640=
Coding: c.1920T>C
MANE Select: NM_001966
dbSNP: rs1166523943
Type: single nucleotide variant
Location: chr3:185192478 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.07

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

Disease context

EHHADH-related disorder

Similar variants

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
EHHADH p.Gly155Arg 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-ala640 (accessed [today's date]).

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