Is ABCA12 p.Val2273= (c.6819A>G) pathogenic?

ABCA12 p.Val2273= (c.6819A>G) is classified Benign/Likely benign in ABCA12 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-28). Rare (popmax 0.674%, afr); Associated with Congenital ichthyosis of skin.

What condition is associated with ABCA12 p.Val2273= (c.6819A>G)?

ABCA12 p.Val2273= (c.6819A>G) is associated with Congenital ichthyosis of skin (ClinVar).

How common is ABCA12 p.Val2273= (c.6819A>G) in the general population?

ABCA12 p.Val2273= (c.6819A>G) is rare (popmax 0.674%, afr) (gnomAD).

ABCA12 p.Val2273=

c.6819A>G · rs139505019 · VCV334224

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.674%, 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 -1.8	GERP -4.7
Overall
CADD	6.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.674% African / African-American · 506/75,042 alleles

Filtering AF 0.626% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.606%

Overall 0.0445% 719/1,614,170 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.674%	148
Middle Eastern	0.115%	866
Admixed American	0.0966%	1,035
Remaining individualsnot grpmax-eligible	0.0656%	1,525
East Asian	0.0134%	7,479
European (non-Finnish)	0.00847%	11,800
South Asian	0.0011%	91,084

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.Val2273=
Coding: c.6819A>G
MANE Select: NM_173076
dbSNP: rs139505019
Type: single nucleotide variant
Location: chr2:214950912 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32
Residue 2273: 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-val2273 (accessed [today's date]).

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