Is ABCA12 p.Lys613fs (c.1836dup) pathogenic?

ABCA12 p.Lys613fs (c.1836dup) is classified Likely pathogenic in ABCA12 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-09). Associated with autosomal recessive congenital ichthyosis 4A.

What condition is associated with ABCA12 p.Lys613fs (c.1836dup)?

ABCA12 p.Lys613fs (c.1836dup) is associated with autosomal recessive congenital ichthyosis 4A, autosomal recessive congenital ichthyosis 4B (ClinVar).

How is Lamellar ichthyosis inherited?

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

ABCA12 p.Lys613fs

c.1836dup · VCV3585391

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

autosomal recessive congenital ichthyosis 4A

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 15 of 53
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.07	GERP -1.7, phastCons 0.96

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

Variant & gene context

Gene: ABCA12
Protein: p.Lys613fs
Coding: c.1836dup
MANE Select: NM_173076
Type: Duplication
Location: chr2:215015609 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32
Residue 613: a UniProt-annotated variant site (in arci4b)

Full ABCA12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive congenital ichthyosis 4A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive congenital ichthyosis 4B

For Lamellar ichthyosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

ABCA12 p.Leu640fs Likely pathogenic ★★ same condition
ABCA12 c.2592+2dup Uncertain significance ★ same condition
ABCA12 c.4978-70_4978-2dup Uncertain significance ★ same condition
ABCA12 p.Ile1915fs Pathogenic same condition
ABCA12 c.985+1G>A Likely pathogenic ★★ same condition
ABCA12 p.Arg1297Ter Pathogenic ★★ same condition
ABCA12 p.Arg1514Cys Pathogenic ★★ same condition
ABCA12 p.Arg1514His 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/abca12-p-lys613fs (accessed [today's date]).

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