Is ABCA12 p.Ile1647= (c.4941C>T) pathogenic?

ABCA12 p.Ile1647= (c.4941C>T) is classified Benign in ABCA12 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). Low-frequency (popmax 2.51%, afr); Associated with Congenital ichthyosis of skin.

What condition is associated with ABCA12 p.Ile1647= (c.4941C>T)?

ABCA12 p.Ile1647= (c.4941C>T) is associated with Congenital ichthyosis of skin (ClinVar).

How common is ABCA12 p.Ile1647= (c.4941C>T) in the general population?

ABCA12 p.Ile1647= (c.4941C>T) is low-frequency (popmax 2.51%, afr) (gnomAD).

ABCA12 p.Ile1647=

c.4941C>T · rs75693572 · VCV334239

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.51%, 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 -3.4	GERP -4.6
Overall
CADD	2.395	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.51% African / African-American · 1,879/74,992 alleles

Filtering AF 2.41% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.37%

Overall 0.143% 2,306/1,613,982 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.51%	40
Admixed American	0.247%	405
Remaining individualsnot grpmax-eligible	0.198%	504
Middle Eastern	0.0495%	2,020
Finnishnot grpmax-eligible	0.0203%	4,924
East Asian	0.0134%	7,477
European (non-Finnish)	0.0111%	9,007
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,802

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.Ile1647=
Coding: c.4941C>T
MANE Select: NM_173076
dbSNP: rs75693572
Type: single nucleotide variant
Location: chr2:214978840 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32
Residue 1647: 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 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-ile1647 (accessed [today's date]).

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