Is ABCD4 p.Phe387fs (c.1158dup) pathogenic?

ABCD4 p.Phe387fs (c.1158dup) is classified Pathogenic in ABCD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-25). Absent from gnomAD; Associated with methylmalonic acidemia with homocystinuria, type cblJ.

What condition is associated with ABCD4 p.Phe387fs (c.1158dup)?

ABCD4 p.Phe387fs (c.1158dup) is associated with methylmalonic acidemia with homocystinuria, type cblJ (ClinVar).

How common is ABCD4 p.Phe387fs (c.1158dup) in the general population?

ABCD4 p.Phe387fs (c.1158dup) is absent from gnomAD (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.Phe387fs

c.1158dup · rs2505338898 · VCV2752020

Pathogenic Single submitter

Classification

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

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 12 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.5, 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: ABCD4
Protein: p.Phe387fs
Coding: c.1158dup
MANE Select: NM_005050
dbSNP: rs2505338898
Type: Duplication
Location: chr14:74290459 (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.Asp406fs Pathogenic ★ same condition
ABCD4 p.Leu257fs Likely pathogenic ★ same condition
ABCD4 p.Thr276fs Likely pathogenic ★ same condition
ABCD4 p.Val3fs Pathogenic ★ same condition
ABCD4 c.1507-3_1507-2dup Uncertain significance ★ same condition
ABCD4 c.1420-11dup Benign ★ same condition
ABCD4 c.542+1G>T Pathogenic ★★ same condition
ABCD4 p.Ala237fs 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/abcd4-p-phe387fs (accessed [today's date]).

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