Is ABCA12 p.Pro1011= (c.3033A>G) pathogenic?

ABCA12 p.Pro1011= (c.3033A>G) is classified Benign in ABCA12 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 34.6%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Congenital ichthyosis of skin.

What condition is associated with ABCA12 p.Pro1011= (c.3033A>G)?

ABCA12 p.Pro1011= (c.3033A>G) is associated with Congenital ichthyosis of skin, autosomal recessive congenital ichthyosis 4B, autosomal recessive congenital ichthyosis 4A (ClinVar).

ABCA12 p.Pro1011=

Q: How common is ABCA12 p.Pro1011= (c.3033A>G) in the general population?

ABCA12 p.Pro1011= (c.3033A>G) is common (popmax 34.6%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3033A>G · rs10498030 · VCV262825

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 34.6%, eas) — too common for a highly-penetrant pathogenic allele

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 0.043	GERP -1.7, phastCons 0.97
Overall
CADD	7.674	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 34.6% East Asian · 15,500/44,862 alleles

Filtering AF 34.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 33.9%

Overall 24.1% 389,606/1,613,940 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	38.2%	3
East Asiangrpmax	34.6%	3
Finnishnot grpmax-eligible	34.3%	3
European (non-Finnish)	25.4%	4
Remaining individualsnot grpmax-eligible	23.7%	4
Middle Eastern	22%	5
Ashkenazi Jewishnot grpmax-eligible	20.3%	5
South Asian	17.9%	6
Admixed American	17.2%	6
African / African-American	4.1%	24

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro1011=
Coding: c.3033A>G
MANE Select: NM_173076
dbSNP: rs10498030
Type: single nucleotide variant
Location: chr2:215000851 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32
Residue 1011: 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

Also linked: autosomal recessive congenital ichthyosis 4B autosomal recessive congenital ichthyosis 4A

Similar variants

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.Arg1950Ter 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-pro1011 (accessed [today's date]).

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