Is ADNP p.Arg730Ter (c.2188C>T) pathogenic?

ADNP p.Arg730Ter (c.2188C>T) is classified Pathogenic/Likely pathogenic in ADNP (ClinVar, Multiple submitters, 24 submitters; last evaluated 2025-02-11). Absent from gnomAD v4.1; Associated with ADNP-related disorder.

What condition is associated with ADNP p.Arg730Ter (c.2188C>T)?

ADNP p.Arg730Ter (c.2188C>T) is associated with ADNP-related disorder, stereotypic movement disorder, hypothyroidism (ClinVar).

How common is ADNP p.Arg730Ter (c.2188C>T) in the general population?

ADNP p.Arg730Ter (c.2188C>T) is absent from gnomAD v4.1 (gnomAD).

ADNP p.Arg730Ter

c.2188C>T · rs886041116 · VCV279598

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 24 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

ADNP-related disorder

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	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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP -0.091, phastCons 1
Overall
CADD	37.0	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: ADNP
Protein: p.Arg730Ter
Coding: c.2188C>T
MANE Select: NM_001282531
dbSNP: rs886041116
Type: single nucleotide variant
Location: chr20:50892526 (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: stereotypic movement disorder hypothyroidism corpus callosum, agenesis of ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder

Similar variants

ADNP p.Arg730Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
ADNP p.Arg730fs Pathogenic ★ same residue
ADNP p.Arg730Pro Uncertain significance ★ ⚠ same residue
ADNP p.Arg173Ter Pathogenic ★★ same condition
ADNP p.Arg225Ter Pathogenic/Likely pathogenic ★★ same condition
ADNP p.Arg306Ter Pathogenic/Likely pathogenic ★★ same condition
ADNP p.Ser738Ter Pathogenic ★★ same condition
ADNP p.Trp446Ter 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-arg730ter (accessed [today's date]).

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