Is ABCD4 p.Val3fs (c.7dup) pathogenic?

ABCD4 p.Val3fs (c.7dup) is classified Pathogenic in ABCD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-23). Very rare (popmax 0.00227%, eas); Associated with methylmalonic acidemia with homocystinuria, type cblJ.

What condition is associated with ABCD4 p.Val3fs (c.7dup)?

ABCD4 p.Val3fs (c.7dup) is associated with methylmalonic acidemia with homocystinuria, type cblJ (ClinVar).

How common is ABCD4 p.Val3fs (c.7dup) in the general population?

ABCD4 p.Val3fs (c.7dup) is very rare (popmax 0.00227%, eas) (gnomAD).

How is Methylmalonic acidemia with homocystinuria inherited?

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

ABCD4 p.Val3fs

c.7dup · rs2505983851 · VCV2784087

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00227%, eas)

Conditions

methylmalonic acidemia with homocystinuria, type cblJ

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 1 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.83	GERP -2.4

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00227% East Asian · 1/44,066 alleles

Overall 6.87e-05% 1/1,455,244 alleles · very rare

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: ABCD4
Protein: p.Val3fs
Coding: c.7dup
MANE Select: NM_005050
dbSNP: rs2505983851
Type: Duplication
Location: chr14:74302905 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.18 · 4 PDB

Full ABCD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

methylmalonic acidemia with homocystinuria, type cblJ — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Methylmalonic acidemia with homocystinuria (Orphanet):

Inheritance: Autosomal recessive, X-linked recessive
Onset: All ages

Similar variants

ABCD4 p.Val3= Likely benign ★ same residue
ABCD4 p.Asp406fs Pathogenic ★ same condition
ABCD4 p.Leu257fs Likely pathogenic ★ same condition
ABCD4 p.Phe387fs Pathogenic ★ same condition
ABCD4 p.Thr276fs Likely pathogenic ★ same condition
ABCD4 c.1507-3_1507-2dup Uncertain significance ★ same condition
ABCD4 p.Val3Gly Uncertain significance ★ ⚠ same residue
ABCD4 c.1420-11dup Benign ★ 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/abcd4-p-val3fs (accessed [today's date]).

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