Is ABCA12 p.Val2463= (c.7389G>A) pathogenic?

ABCA12 p.Val2463= (c.7389G>A) is classified Conflicting classifications of pathogenicity in ABCA12 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-23). Ultra-rare (popmax 0.0602%, eas); Associated with Congenital ichthyosis of skin.

What condition is associated with ABCA12 p.Val2463= (c.7389G>A)?

ABCA12 p.Val2463= (c.7389G>A) is associated with Congenital ichthyosis of skin (ClinVar).

How common is ABCA12 p.Val2463= (c.7389G>A) in the general population?

ABCA12 p.Val2463= (c.7389G>A) is ultra-rare (popmax 0.0602%, eas) (gnomAD).

ABCA12 p.Val2463=

c.7389G>A · rs202031511 · VCV899200

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0602%, eas)

Conditions

Congenital ichthyosis of skin

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.36	donor loss, 47 bp away · masked 0 · deltas
Pangolin	Δ0.29	loss · gain 0.17 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.6	GERP 0.69, phastCons 1
Overall
CADD	11.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0602% East Asian · 27/44,824 alleles

Filtering AF 0.0424% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0365%

Overall 0.00186% 30/1,613,560 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0602%	1,660
Remaining individualsnot grpmax-eligible	0.0016%	62,462
South Asian	0.0011%	91,074
European (non-Finnish)	8.48e-05%	1,179,810

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.Val2463=
Coding: c.7389G>A
MANE Select: NM_173076
dbSNP: rs202031511
Type: single nucleotide variant
Location: chr2:214942972 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32
Residue 2463: the abc transporter 2 domain; 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

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-val2463 (accessed [today's date]).

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