Is ADNP p.Ile22fs (c.64dup) pathogenic?

ADNP p.Ile22fs (c.64dup) is classified Pathogenic/Likely pathogenic in ADNP (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-11-12). Absent from gnomAD v4.1; Associated with ADNP-related disorder.

What condition is associated with ADNP p.Ile22fs (c.64dup)?

ADNP p.Ile22fs (c.64dup) is associated with ADNP-related disorder, ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder (ClinVar).

How common is ADNP p.Ile22fs (c.64dup) in the general population?

ADNP p.Ile22fs (c.64dup) is absent from gnomAD v4.1 (gnomAD).

ADNP p.Ile22fs

c.64dup · rs1982229334 · VCV931423

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,912)

Conditions

ADNP-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,912). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ADNP
Protein: p.Ile22fs
Coding: c.64dup
MANE Select: NM_001282531
dbSNP: rs1982229334
Type: Duplication
Location: chr20:50903932 (GRCh38)
Gene constraint: LOEUF 0.106 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.07

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

Disease context

ADNP-related disorder

Also linked: ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder

Similar variants

ADNP p.Asn905Ter Likely pathogenic ★★ same condition
ADNP p.Ser738fs Pathogenic ★★ same condition
ADNP p.Thr64fs Pathogenic ★★ same condition
ADNP p.Val1084fs Uncertain significance ★★ same condition
ADNP p.Ser141dup Benign/Likely benign ★★ same condition
ADNP p.Asn398Ter Pathogenic ★ same condition
ADNP p.Asp60fs Pathogenic ★ same condition
ADNP p.Asp762fs 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/adnp-p-ile22fs (accessed [today's date]).

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