Is IVD p.Pro232fs (c.693dup) pathogenic?

IVD p.Pro232fs (c.693dup) is classified Likely pathogenic in IVD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-01). Absent from gnomAD; Associated with isovaleric acidemia.

What condition is associated with IVD p.Pro232fs (c.693dup)?

IVD p.Pro232fs (c.693dup) is associated with isovaleric acidemia (ClinVar).

How common is IVD p.Pro232fs (c.693dup) in the general population?

IVD p.Pro232fs (c.693dup) is absent from gnomAD (gnomAD).

How is Isovaleric acidemia inherited?

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

IVD p.Pro232fs

c.693dup · rs2542713682 · VCV1724852

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

isovaleric acidemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.5	GERP 0.59, 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: IVD
Protein: p.Pro232fs
Coding: c.693dup
MANE Select: NM_002225
dbSNP: rs2542713682
Type: Duplication
Location: chr15:40412995 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.25 · 5 PDB

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

Disease context

isovaleric acidemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Isovaleric acidemia (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

IVD p.Pro291fs Pathogenic ★★ same condition
IVD p.Ser43fs Pathogenic/Likely pathogenic ★★ same condition
IVD p.Thr223fs Pathogenic/Likely pathogenic ★★ same condition
IVD p.Ala218fs Likely pathogenic ★ same condition
IVD p.Ala224fs Pathogenic ★ same condition
IVD p.Arg411delinsGlyLeuGlyProAlaArgTer Pathogenic ★ same condition
IVD p.Asn249Ter Pathogenic ★ same condition
IVD p.Glu143_Ala144insTer Likely pathogenic ★ 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/ivd-p-pro232fs (accessed [today's date]).

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