Is ABCA12 p.Leu641= (c.1923G>C) pathogenic?

ABCA12 p.Leu641= (c.1923G>C) is classified Benign/Likely benign in ABCA12 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-03-01). Rare (popmax 0.711%, nfe); Associated with Congenital ichthyosis of skin.

What condition is associated with ABCA12 p.Leu641= (c.1923G>C)?

ABCA12 p.Leu641= (c.1923G>C) is associated with Congenital ichthyosis of skin (ClinVar).

How common is ABCA12 p.Leu641= (c.1923G>C) in the general population?

ABCA12 p.Leu641= (c.1923G>C) is rare (popmax 0.711%, nfe) (gnomAD).

ABCA12 p.Leu641=

c.1923G>C · rs79664364 · VCV334260

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.711%, nfe)

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 -1.5	GERP -2.7
Overall
CADD	3.054	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.711% European (non-Finnish) · 8,385/1,179,938 alleles

Filtering AF 0.698% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.693%

Overall 0.594% 9,593/1,614,032 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.711%	141
Remaining individualsnot grpmax-eligible	0.637%	157
Ashkenazi Jewishnot grpmax-eligible	0.595%	168
Admixed American	0.556%	180
Middle Eastern	0.346%	289
Finnishnot grpmax-eligible	0.223%	448
African / African-American	0.125%	798
South Asian	0.0439%	2,277
East Asian	0.00446%	22,436

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.Leu641=
Coding: c.1923G>C
MANE Select: NM_173076
dbSNP: rs79664364
Type: single nucleotide variant
Location: chr2:215015523 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32
Residue 641: 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-leu641 (accessed [today's date]).

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