Is ABCA12 p.Val296= (c.888G>A) pathogenic?

ABCA12 p.Val296= (c.888G>A) is classified Benign in ABCA12 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 43.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Congenital ichthyosis of skin.

What condition is associated with ABCA12 p.Val296= (c.888G>A)?

ABCA12 p.Val296= (c.888G>A) is associated with Congenital ichthyosis of skin (ClinVar).

ABCA12 p.Val296=

Q: How common is ABCA12 p.Val296= (c.888G>A) in the general population?

ABCA12 p.Val296= (c.888G>A) is common (popmax 43.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.888G>A · rs17501837 · VCV262834

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 43.8%, 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 0.57	GERP -2.5, phastCons 0.53
Overall
CADD	4.644	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 43.8% East Asian · 19,613/44,812 alleles

Filtering AF 43.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 43%

Overall 20.8% 334,939/1,612,510 alleles · common exomes 305,910/1,460,418 · genomes 29,029/152,092 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	43.8%	2
Admixed American	26.6%	4
Amishnot grpmax-eligible	24.1%	4
Remaining individualsnot grpmax-eligible	20.9%	5
European (non-Finnish)	20.9%	5
Ashkenazi Jewishnot grpmax-eligible	19.6%	5
Finnishnot grpmax-eligible	16.7%	6
Middle Eastern	15%	7
African / African-American	14.6%	7
South Asian	13.1%	8

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.Val296=
Coding: c.888G>A
MANE Select: NM_173076
dbSNP: rs17501837
Type: single nucleotide variant
Location: chr2:215037050 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32

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-val296 (accessed [today's date]).

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