Is AP1G1 p.Lys156= (c.468G>A) pathogenic?

AP1G1 p.Lys156= (c.468G>A) is classified Likely pathogenic in AP1G1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-10-13). Absent from gnomAD v4.1; Associated with Usmani-Riazuddin syndrome, autosomal dominant.

What condition is associated with AP1G1 p.Lys156= (c.468G>A)?

AP1G1 p.Lys156= (c.468G>A) is associated with Usmani-Riazuddin syndrome, autosomal dominant (ClinVar).

How common is AP1G1 p.Lys156= (c.468G>A) in the general population?

AP1G1 p.Lys156= (c.468G>A) is absent from gnomAD v4.1 (gnomAD).

AP1G1 p.Lys156=

c.468G>A · VCV4082056

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Usmani-Riazuddin syndrome, autosomal dominant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.95	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.77	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AP1G1
Protein: p.Lys156=
Coding: c.468G>A
MANE Select: NM_001128
Type: single nucleotide variant
Location: chr16:71773221 (GRCh38)
Gene constraint: LOEUF 0.113 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.56 · 1 PDB

Full AP1G1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Usmani-Riazuddin syndrome, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AP1G1 p.Arg15Trp Likely pathogenic ★★ same condition
AP1G1 p.Arg416Ter Pathogenic ★★ same condition
AP1G1 p.Arg46Ter Uncertain significance ★★ same condition
AP1G1 c.1497+1G>A Pathogenic ★ same condition
AP1G1 c.1872+1G>T Pathogenic ★ same condition
AP1G1 c.-2G>A Likely pathogenic ★ same condition
AP1G1 p.Arg248Ter Pathogenic ★ same condition
AP1G1 p.Gln273Ter Likely 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/ap1g1-p-lys156 (accessed [today's date]).

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