Is ABCA12 p.Arg1950Ter (c.5848C>T) pathogenic?

ABCA12 p.Arg1950Ter (c.5848C>T) is classified Pathogenic in ABCA12 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-09-25). Very rare (popmax 0.00223%, eas); Associated with autosomal recessive congenital ichthyosis 4A.

What condition is associated with ABCA12 p.Arg1950Ter (c.5848C>T)?

ABCA12 p.Arg1950Ter (c.5848C>T) is associated with autosomal recessive congenital ichthyosis 4A, autosomal recessive congenital ichthyosis 4B (ClinVar).

How common is ABCA12 p.Arg1950Ter (c.5848C>T) in the general population?

ABCA12 p.Arg1950Ter (c.5848C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Lamellar ichthyosis inherited?

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

ABCA12 p.Arg1950Ter

c.5848C>T · rs375437551 · VCV2203257

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

autosomal recessive congenital ichthyosis 4A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 39 of 53
Splicing
SpliceAI	Δ0.37	donor loss · deltas
Pangolin	Δ0.48	loss · gain 0.47 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.1	GERP 0.39, phastCons 0.99
Overall
CADD	43.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,860 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.00031% 5/1,613,630 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,860
Remaining individualsnot grpmax-eligible	0.0016%	62,476
African / African-American	0.00134%	74,876
European (non-Finnish)	0.00017%	589,908

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: ABCA12
Protein: p.Arg1950Ter
Coding: c.5848C>T
MANE Select: NM_173076
dbSNP: rs375437551
Type: single nucleotide variant
Location: chr2:214966884 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32
Residue 1950: a UniProt-annotated variant site (in arci4b); a UniProt-annotated variant site (in arci4b; uncertain significance)

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.Arg1950Gln Uncertain significance ★★ ⚠ same residue
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
ABCA12 p.Arg1515Ter Pathogenic ★★ same condition
ABCA12 p.Arg1960Ter Likely pathogenic ★★ same condition
ABCA12 p.Arg2204Ter 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-arg1950ter (accessed [today's date]).

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