Is AP1B1 p.Ala783= (c.2349G>A) pathogenic?

AP1B1 p.Ala783= (c.2349G>A) is classified Benign in AP1B1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-07-14). Common (popmax 68.4%, eas) — too common for a highly-penetrant pathogenic allele; Associated with ichthyosiform erythroderma, corneal involvement, and hearing loss.

What condition is associated with AP1B1 p.Ala783= (c.2349G>A)?

AP1B1 p.Ala783= (c.2349G>A) 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.Ala783=

Q: How common is AP1B1 p.Ala783= (c.2349G>A) in the general population?

AP1B1 p.Ala783= (c.2349G>A) is common (popmax 68.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2349G>A · rs174765 · VCV1192401

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 68.4%, eas) — 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 -13	GERP -3.5
Overall
CADD	0.681	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 68.4% East Asian · 30,678/44,840 alleles

Filtering AF 67.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 67.5%

Overall 55.5% 895,488/1,612,808 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	68.4%	1
Finnishnot grpmax-eligible	58.1%	2
European (non-Finnish)	56.7%	2
Remaining individualsnot grpmax-eligible	54%	2
Amishnot grpmax-eligible	53.8%	2
South Asian	51.4%	2
Ashkenazi Jewishnot grpmax-eligible	49.3%	2
Middle Eastern	49%	2
Admixed American	45.2%	2
African / African-American	44.8%	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.Ala783=
Coding: c.2349G>A
MANE Select: NM_001127
dbSNP: rs174765
Type: single nucleotide variant
Location: chr22:29331877 (GRCh38)
Gene constraint: LOEUF 0.476 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 82.46 · 20 PDB

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.Ala783Thr Uncertain significance ★ ⚠ same residue
AP1B1 p.Leu68= 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-ala783 (accessed [today's date]).

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