Is EHHADH p.Ser397fs (c.1189dup) pathogenic?

EHHADH p.Ser397fs (c.1189dup) is classified Likely benign in EHHADH (ClinVar, No assertion criteria, 1 submitter). No gnomAD frequency available for this variant; Associated with Fanconi renotubular syndrome 3.

What condition is associated with EHHADH p.Ser397fs (c.1189dup)?

EHHADH p.Ser397fs (c.1189dup) is associated with Fanconi renotubular syndrome 3 (ClinVar).

How common is EHHADH p.Ser397fs (c.1189dup) in the general population?

EHHADH p.Ser397fs (c.1189dup) is no gnomAD frequency available for this variant (gnomAD).

How is Primary Fanconi renotubular syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

EHHADH p.Ser397fs

c.1189dup · rs2474822687 · VCV977889

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Fanconi renotubular syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (7 of 7) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EHHADH
Protein: p.Ser397fs
Coding: c.1189dup
MANE Select: NM_001966
dbSNP: rs2474822687
Type: Duplication
Location: chr3:185193208 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.07
Residue 397: the '3-hydroxyacyl-coa dehydrogenase' region

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

Disease context

Fanconi renotubular syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary Fanconi renotubular syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood, Infancy

Similar variants

EHHADH p.Asp42Glu Uncertain significance ★★ ⚠ same condition
EHHADH p.Leu365Val Uncertain significance ★★ ⚠ same condition
EHHADH p.Glu3Lys Likely pathogenic ★ ⚠ same condition
EHHADH p.Ala39_Val40insTer Conflicting classifications of pathogenicity ★ same condition
EHHADH p.Arg551Ter Uncertain significance ★ same condition
EHHADH p.Arg622His Uncertain significance ★ ⚠ same condition
EHHADH p.Arg633Ser Uncertain significance ★ ⚠ same condition
EHHADH p.Gln230Ter 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-ser397fs (accessed [today's date]).

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