Is ADNP p.Arg730Pro (c.2189G>C) pathogenic?

ADNP p.Arg730Pro (c.2189G>C) is classified Uncertain significance in ADNP (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-05). AlphaMissense: likely pathogenic (0.8077); Absent from gnomAD v4.1.

How common is ADNP p.Arg730Pro (c.2189G>C) in the general population?

ADNP p.Arg730Pro (c.2189G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADNP p.Arg730Pro (c.2189G>C)?

AlphaMissense predicts likely pathogenic (score 0.8077) — an in-silico prediction, not a clinical call.

ADNP p.Arg730Pro

c.2189G>C · rs377051194 · VCV1309778

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8077 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8077	likely pathogenic
REVEL	0.253	benign-leaning
SaProt	LLR -5.98	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.9	GERP 0.93, phastCons 1
Regional constraint	o/e 1.29	unconstrained · MANE · 195 bp · p 0.011 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Arg730Pro
Coding: c.2189G>C
MANE Select: NM_001282531
dbSNP: rs377051194
Type: single nucleotide variant
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

Similar variants

ADNP p.Arg730Ter Pathogenic/Likely pathogenic ★★ same residue
ADNP p.Arg730Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
ADNP p.Arg730fs Pathogenic ★ same residue
ADNP p.Arg173Ter Pathogenic ★★ same type
ADNP p.Arg216Ter Pathogenic ★★ same type
ADNP p.Arg225Ter Pathogenic/Likely pathogenic ★★ same type
ADNP p.Arg306Ter Pathogenic/Likely pathogenic ★★ same type
ADNP p.Ser738Ter Pathogenic ★★ same type

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-arg730pro (accessed [today's date]).

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