Is IVD p.Asp241= (c.723C>T) pathogenic?

IVD p.Asp241= (c.723C>T) is classified Benign in IVD (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 13.3%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with isovaleric acidemia.

What condition is associated with IVD p.Asp241= (c.723C>T)?

IVD p.Asp241= (c.723C>T) is associated with isovaleric acidemia (ClinVar).

How is Isovaleric acidemia inherited?

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

IVD p.Asp241=

Q: How common is IVD p.Asp241= (c.723C>T) in the general population?

IVD p.Asp241= (c.723C>T) is common (popmax 13.3%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.723C>T · rs2229312 · VCV94057

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 13.3%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

isovaleric acidemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.104	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 0.56, phastCons 1
Overall
CADD	12.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 13.3% European (non-Finnish) · 156,840/1,178,296 alleles

Filtering AF 13.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.2%

Overall 12.6% 203,066/1,612,232 alleles · common exomes 185,480/1,459,976 · genomes 17,586/152,256 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	20.9%	5
Ashkenazi Jewishnot grpmax-eligible	14.1%	7
European (non-Finnish)grpmax	13.3%	8
Remaining individualsnot grpmax-eligible	12.7%	8
Middle Eastern	11.1%	9
South Asian	10%	10
Amishnot grpmax-eligible	8.44%	12
African / African-American	8.21%	12
Admixed American	7.1%	14
East Asian	1%	100

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp241=
Coding: c.723C>T
MANE Select: NM_002225
dbSNP: rs2229312
Type: single nucleotide variant
Location: chr15:40413026 (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.Asp241Asn Uncertain significance ★ ⚠ 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
IVD c.286+5G>T Likely pathogenic ★★ same condition
IVD c.287-1G>A Pathogenic/Likely pathogenic ★★ same condition
IVD c.287-2A>G Pathogenic/Likely pathogenic ★★ same condition
IVD c.456+2T>C 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-asp241 (accessed [today's date]).

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