Is ABCA12 p.Ala2080= (c.6240A>C) pathogenic?

ABCA12 p.Ala2080= (c.6240A>C) is classified Uncertain significance in ABCA12 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Absent from gnomAD v4.1; Associated with Congenital ichthyosis of skin.

What condition is associated with ABCA12 p.Ala2080= (c.6240A>C)?

ABCA12 p.Ala2080= (c.6240A>C) is associated with Congenital ichthyosis of skin (ClinVar).

How common is ABCA12 p.Ala2080= (c.6240A>C) in the general population?

ABCA12 p.Ala2080= (c.6240A>C) is absent from gnomAD v4.1 (gnomAD).

ABCA12 p.Ala2080=

c.6240A>C · rs947649130 · VCV896530

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.82	GERP 0.3, phastCons 1
Overall
CADD	6.865	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCA12
Protein: p.Ala2080=
Coding: c.6240A>C
MANE Select: NM_173076
dbSNP: rs947649130
Type: single nucleotide variant
Location: chr2:214955355 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32
Residue 2080: 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 p.Ala2080Thr Uncertain significance ★ ⚠ same residue
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

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-ala2080 (accessed [today's date]).

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