Is AP1B1 p.Leu68= (c.204A>G) pathogenic?

AP1B1 p.Leu68= (c.204A>G) is classified Benign in AP1B1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2021-07-14). Common (popmax 84%, afr) — too common for a highly-penetrant pathogenic allele; Associated with ichthyosiform erythroderma, corneal involvement, and hearing loss.

What condition is associated with AP1B1 p.Leu68= (c.204A>G)?

AP1B1 p.Leu68= (c.204A>G) is associated with ichthyosiform erythroderma, corneal involvement, and hearing loss (ClinVar).

How is KID syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

AP1B1 p.Leu68=

Q: How common is AP1B1 p.Leu68= (c.204A>G) in the general population?

AP1B1 p.Leu68= (c.204A>G) is common (popmax 84%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.204A>G · rs2072051 · VCV1192402

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 84%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

ichthyosiform erythroderma, corneal involvement, and hearing loss

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 0.013	GERP -2.9, phastCons 0.78
Overall
CADD	9.56	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 84% African / African-American · 62,998/75,012 alleles

Filtering AF 83.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 83.2%

Overall 57.4% 926,626/1,613,406 alleles · common exomes 830,646/1,461,240 · genomes 95,980/152,166 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	84%	1
East Asian	71.5%	1
Finnishnot grpmax-eligible	61.7%	2
Amishnot grpmax-eligible	58.4%	2
Remaining individualsnot grpmax-eligible	56.7%	2
European (non-Finnish)	56.1%	2
South Asian	54.7%	2
Middle Eastern	48.4%	2
Admixed American	47.3%	2
Ashkenazi Jewishnot grpmax-eligible	43.3%	2

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: AP1B1
Protein: p.Leu68=
Coding: c.204A>G
MANE Select: NM_001127
dbSNP: rs2072051
Type: single nucleotide variant
Location: chr22:29359899 (GRCh38)
Gene constraint: LOEUF 0.476 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 82.46 · 20 PDB
Residue 68: an α-helix

Full AP1B1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ichthyosiform erythroderma, corneal involvement, and hearing loss — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For KID syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: Neonatal

Similar variants

AP1B1 p.Leu68Arg Uncertain significance ★ ⚠ same residue
AP1B1 p.Ala783= Benign ★★ same condition
AP1B1 p.Met1Thr Likely pathogenic ★ same condition
AP1B1 p.Leu223Pro Uncertain significance ★ ⚠ same condition
AP1B1 p.Val176= Uncertain significance ★ same condition
AP1B1 c.38-1G>A Pathogenic same condition
AP1B1 p.Arg108Trp Pathogenic same condition
AP1B1 p.Cys144Arg 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/ap1b1-p-leu68 (accessed [today's date]).

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