Is ADNP p.Arg730fs (c.2189del) pathogenic?

ADNP p.Arg730fs (c.2189del) is classified Pathogenic in ADNP (ClinVar, Single submitter, 2 submitters; last evaluated 2024-10-09). Absent from gnomAD; Associated with ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder.

How common is ADNP p.Arg730fs (c.2189del) in the general population?

ADNP p.Arg730fs (c.2189del) is absent from gnomAD (gnomAD).

ADNP p.Arg730fs

Q: What condition is associated with ADNP p.Arg730fs (c.2189del)?

ADNP p.Arg730fs (c.2189del) is associated with ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder (ClinVar).

c.2189del · rs2489790262 · VCV3033209

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum 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	escapes	premature termination codon in the last exon (6 of 6) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -9.1	GERP -3.8

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Arg730fs
Coding: c.2189del
MANE Select: NM_001282531
dbSNP: rs2489790262
Type: Deletion
Location: chr20:50892525 (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 multiple congenital anomalies - intellectual disability - autism spectrum disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ADNP p.Arg730Ter Pathogenic/Likely pathogenic ★★ same residue
ADNP p.Arg730Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
ADNP p.Leu831fs Pathogenic/Likely pathogenic ★★ same condition
ADNP p.Lys773fs Pathogenic ★★ same condition
ADNP p.Lys829fs Pathogenic/Likely pathogenic ★★ same condition
ADNP p.Ser955fs Pathogenic/Likely pathogenic ★★ same condition
ADNP p.Thr718_Tyr719insTer Pathogenic ★★ same condition
ADNP p.Val180fs 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-arg730fs (accessed [today's date]).

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