Is IVD p.Arg50= (c.150T>A) pathogenic?

IVD p.Arg50= (c.150T>A) is classified Conflicting classifications of pathogenicity in IVD (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2023-12-21). Very rare (popmax 0.00331%, nfe); Associated with isovaleric acidemia.

What condition is associated with IVD p.Arg50= (c.150T>A)?

IVD p.Arg50= (c.150T>A) is associated with isovaleric acidemia (ClinVar).

How common is IVD p.Arg50= (c.150T>A) in the general population?

IVD p.Arg50= (c.150T>A) is very rare (popmax 0.00331%, nfe) (gnomAD).

How is Isovaleric acidemia inherited?

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

IVD p.Arg50=

c.150T>A · rs762440985 · VCV510860

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00331%, nfe)

Conditions

isovaleric acidemia

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 -1.2	GERP -4.5, phastCons 0.002
Overall
CADD	9.888	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00331% European (non-Finnish) · 39/1,179,852 alleles

Filtering AF 0.00247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.00254% 41/1,613,894 alleles · very rare exomes 40/1,461,680 · genomes 1/152,214 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00331%	30,253
Remaining individualsnot grpmax-eligible	0.0032%	31,243

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: IVD
Protein: p.Arg50=
Coding: c.150T>A
MANE Select: NM_002225
dbSNP: rs762440985
Type: single nucleotide variant
Location: chr15:40407641 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.25 · 5 PDB
Residue 50: an α-helix

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.Arg50Cys Pathogenic/Likely pathogenic ★★ same residue
IVD p.Arg50His Pathogenic/Likely pathogenic ★★ same residue
IVD p.Arg50Leu Likely pathogenic ★★ same residue
IVD p.Arg50Pro Pathogenic/Likely pathogenic ★★ same residue
IVD p.Arg50Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
IVD c.144+1G>A Likely pathogenic ★★ same condition
IVD c.144+1G>C Pathogenic ★★ same condition
IVD c.286+2T>C Pathogenic/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-arg50 (accessed [today's date]).

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