Is ABCA12 p.Ala708= (c.2124A>G) pathogenic?

ABCA12 p.Ala708= (c.2124A>G) is classified Benign in ABCA12 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 62.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Congenital ichthyosis of skin.

What condition is associated with ABCA12 p.Ala708= (c.2124A>G)?

ABCA12 p.Ala708= (c.2124A>G) is associated with Congenital ichthyosis of skin (ClinVar).

ABCA12 p.Ala708=

Q: How common is ABCA12 p.Ala708= (c.2124A>G) in the general population?

ABCA12 p.Ala708= (c.2124A>G) is common (popmax 62.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2124A>G · rs10198064 · VCV262823

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 62.2%, afr) — 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 -1.2	GERP -3.9, phastCons 0.001
Overall
CADD	0.203	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 62.2% African / African-American · 46,568/74,866 alleles

Filtering AF 61.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 61.5%

Overall 12.4% 199,533/1,613,406 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	62.2%	2
Admixed American	25.9%	4
Middle Eastern	23.3%	4
South Asian	16.5%	6
Amishnot grpmax-eligible	14.5%	7
Remaining individualsnot grpmax-eligible	14.2%	7
Ashkenazi Jewishnot grpmax-eligible	12.7%	8
European (non-Finnish)	8.79%	11
East Asian	5.43%	18
Finnishnot grpmax-eligible	3.31%	30

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.Ala708=
Coding: c.2124A>G
MANE Select: NM_173076
dbSNP: rs10198064
Type: single nucleotide variant
Location: chr2:215011647 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32
Residue 708: 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

Similar variants

ABCA12 p.Ala708Glu Uncertain significance ★ ⚠ same residue
ABCA12 p.Ala708Val 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

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-ala708 (accessed [today's date]).

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