Is AP1S2 p.Gln36Ter (c.106C>T) pathogenic?

AP1S2 p.Gln36Ter (c.106C>T) is classified Pathogenic in AP1S2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2006-12-01). Absent from gnomAD v4.1; Associated with syndromic X-linked intellectual disability 5.

What condition is associated with AP1S2 p.Gln36Ter (c.106C>T)?

AP1S2 p.Gln36Ter (c.106C>T) is associated with syndromic X-linked intellectual disability 5 (ClinVar).

How common is AP1S2 p.Gln36Ter (c.106C>T) in the general population?

AP1S2 p.Gln36Ter (c.106C>T) is absent from gnomAD v4.1 (gnomAD).

AP1S2 p.Gln36Ter

c.106C>T · rs104894739 · VCV10777

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

syndromic X-linked intellectual disability 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 6
REVEL	0.844	moderately pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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: AP1S2
Protein: p.Gln36Ter
Coding: c.106C>T
MANE Select: NM_001272071
dbSNP: rs104894739
Type: single nucleotide variant
Location: chrX:15852419 (GRCh38)
Structure: AlphaFold pLDDT 94.36

Full AP1S2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

syndromic X-linked intellectual disability 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AP1S2 p.Gln36Arg Uncertain significance ★ ⚠ same residue
AP1S2 p.Gln36= Likely benign ★ same residue
AP1S2 c.-1+1G>A Pathogenic/Likely pathogenic ★★ same condition
AP1S2 p.Arg52Ter Pathogenic ★★ same condition
AP1S2 p.Gln123Ter Pathogenic ★★ same condition
AP1S2 c.1-3C>A Pathogenic ★ same condition
AP1S2 c.288+1G>A Pathogenic ★ same condition
AP1S2 c.288+5G>A 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/ap1s2-p-gln36ter (accessed [today's date]).

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