Is ABCA12 p.Ser1668fs (c.5001_5010del) pathogenic?

ABCA12 p.Ser1668fs (c.50015010del) is classified Likely pathogenic in ABCA12 (ClinVar, No assertion criteria, 1 submitter). Absent from gnomAD; Associated with autosomal recessive congenital ichthyosis 4A.

What condition is associated with ABCA12 p.Ser1668fs (c.5001_5010del)?

ABCA12 p.Ser1668fs (c.5001_5010del) is associated with autosomal recessive congenital ichthyosis 4A (ClinVar).

How common is ABCA12 p.Ser1668fs (c.5001_5010del) in the general population?

ABCA12 p.Ser1668fs (c.5001_5010del) is absent from gnomAD (gnomAD).

How is Lamellar ichthyosis inherited?

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

ABCA12 p.Ser1668fs

c.5001_5010del · rs2469221127 · VCV2579655

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 33 of 53
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP -1.9, phastCons 0.15

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: ABCA12
Protein: p.Ser1668fs
Coding: c.5001_5010del
MANE Select: NM_173076
dbSNP: rs2469221127
Type: Deletion
Location: chr2:214978434 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32
Residue 1668: 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

For Lamellar ichthyosis (Orphanet):

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

Similar variants

ABCA12 p.Asn528fs Pathogenic/Likely pathogenic ★★ same condition
ABCA12 p.Phe2286fs Pathogenic ★★ same condition
ABCA12 p.Val2442fs Pathogenic ★★ same condition
ABCA12 c.5469_5472del Pathogenic ★ same condition
ABCA12 p.Glu1932fs Likely pathogenic ★ same condition
ABCA12 p.Glu886fs Likely pathogenic ★ same condition
ABCA12 p.Leu217_Leu218insTer Likely pathogenic ★ same condition
ABCA12 p.Met1674fs 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-ser1668fs (accessed [today's date]).

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