Is ABCA12 p.Ser291Argfs (c.(872+1_873-1) pathogenic?

ABCA12 p.Ser291Argfs (c.(872+1873-1) is classified Pathogenic in ABCA12 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2006-11-01). Associated with autosomal recessive congenital ichthyosis 4B.

What condition is associated with ABCA12 p.Ser291Argfs (c.(872+1_873-1)?

ABCA12 p.Ser291Argfs (c.(872+1_873-1) is associated with autosomal recessive congenital ichthyosis 4B (ClinVar).

How is Harlequin ichthyosis inherited?

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

ABCA12 p.Ser291Argfs

c.(872+1_873-1 · VCV2864

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

autosomal recessive congenital ichthyosis 4B

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations

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

Variant & gene context

Gene: ABCA12
Protein: p.Ser291Argfs
Coding: c.(872+1_873-1
MANE Select: NM_173076
Type: Deletion
Location: chr2:None (GRCh37)
Gene constraint: LOEUF 0.582 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32

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

Disease context

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

For Harlequin ichthyosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

ABCA12 p.Asn528fs Pathogenic/Likely pathogenic ★★ same condition
ABCA12 p.Phe2286fs Pathogenic ★★ same condition
ABCA12 p.Val2442fs Pathogenic ★★ same condition
ABCA12 p.Arg1461fs Likely pathogenic ★ same condition
ABCA12 p.Arg248fs Likely pathogenic ★ same condition
ABCA12 p.Glu1932fs Likely pathogenic ★ same condition
ABCA12 p.Leu217_Leu218insTer Likely pathogenic ★ same condition
ABCA12 p.Lys1682fs 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-ser291argfs (accessed [today's date]).

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