Is ABCA12 p.Ala1594= (c.4782C>T) pathogenic?

ABCA12 p.Ala1594= (c.4782C>T) is classified Conflicting classifications of pathogenicity in ABCA12 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.0453%, afr); Associated with Congenital ichthyosis of skin.

What condition is associated with ABCA12 p.Ala1594= (c.4782C>T)?

ABCA12 p.Ala1594= (c.4782C>T) is associated with Congenital ichthyosis of skin (ClinVar).

How common is ABCA12 p.Ala1594= (c.4782C>T) in the general population?

ABCA12 p.Ala1594= (c.4782C>T) is ultra-rare (popmax 0.0453%, afr) (gnomAD).

ABCA12 p.Ala1594=

c.4782C>T · rs146990068 · VCV334241

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0453%, afr)

Conditions

Congenital ichthyosis of skin

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.4	GERP -4.3
Overall
CADD	0.108	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0453% African / African-American · 34/75,002 alleles

Filtering AF 0.0333% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0292%

Overall 0.0232% 374/1,614,002 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0453%	2,206
Admixed American	0.0283%	3,530
European (non-Finnish)	0.0265%	3,770
Remaining individualsnot grpmax-eligible	0.0144%	6,945
South Asian	0.0011%	91,076

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.Ala1594=
Coding: c.4782C>T
MANE Select: NM_173076
dbSNP: rs146990068
Type: single nucleotide variant
Location: chr2:214978999 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32
Residue 1594: a UniProt-annotated variant site (in arci4b)

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

Disease context

Congenital ichthyosis of skin — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCA12 c.6962+5G>A Uncertain significance ★★ same condition
ABCA12 p.Ala1083Gly Uncertain significance ★★ ⚠ same condition
ABCA12 p.Gln2162Lys Uncertain significance ★★ ⚠ same condition
ABCA12 p.Glu2368Lys Uncertain significance ★★ ⚠ same condition
ABCA12 c.1062-8T>A Benign/Likely benign ★★ same condition
ABCA12 c.1287+14G>T Benign/Likely benign ★★ same condition
ABCA12 c.*26G>A Benign ★★ same condition
ABCA12 c.*790A>G Benign ★★ 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-ala1594 (accessed [today's date]).

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