Is AP1S2 c.1-3C>A pathogenic?

AP1S2 c.1-3C>A is classified Pathogenic in AP1S2 (ClinVar, Single submitter, 1 submitter; last evaluated 2015-06-24). Absent from gnomAD v4.1; Associated with syndromic X-linked intellectual disability 5.

What condition is associated with AP1S2 c.1-3C>A?

AP1S2 c.1-3C>A is associated with syndromic X-linked intellectual disability 5 (ClinVar).

How common is AP1S2 c.1-3C>A in the general population?

AP1S2 c.1-3C>A is absent from gnomAD v4.1 (gnomAD).

AP1S2 c.1-3C>A

rs1060499672 · VCV397541

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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/SpliceAI carries the signal.
Splicing
Splice region	acceptor -3	acceptor splice region (-3, within the last 20 intronic nt) · inside the BP7-excluded zone
SpliceAI	Δ0.91	acceptor loss · deltas
Pangolin	Δ0.66	gain · loss 0.60 · SpliceAI calls loss · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Non-coding constraint	—	not assessed · autosomes only, so chrX has no window · absence ≠ unconstrained
Overall
CADD	22.3	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: AP1S2
Coding: c.1-3C>A
MANE Select: NM_001272071
dbSNP: rs1060499672
Type: single nucleotide variant
Location: chrX:15852527 (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 c.-1+1G>A Pathogenic/Likely pathogenic ★★ same condition
AP1S2 p.Arg52Ter Pathogenic ★★ same condition
AP1S2 p.Gln123Ter Pathogenic ★★ same condition
AP1S2 c.288+1G>A Pathogenic ★ same condition
AP1S2 c.288+5G>A Likely pathogenic ★ same condition
AP1S2 c.426+1G>T Pathogenic ★ same condition
AP1S2 p.Arg14Ter Pathogenic ★ same condition
AP1S2 c.*241A>C Uncertain significance ★ 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-c-1-minus-3c-a (accessed [today's date]).

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