Is ADNP p.Arg1007Lys (c.3020G>A) pathogenic?

ADNP p.Arg1007Lys (c.3020G>A) is classified Conflicting classifications of pathogenicity in ADNP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-05-29). AlphaMissense: likely benign (0.0756); Very rare (popmax 0.000169%, nfe); Associated with ADNP-related disorder.

What condition is associated with ADNP p.Arg1007Lys (c.3020G>A)?

ADNP p.Arg1007Lys (c.3020G>A) is associated with ADNP-related disorder (ClinVar).

How common is ADNP p.Arg1007Lys (c.3020G>A) in the general population?

ADNP p.Arg1007Lys (c.3020G>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about ADNP p.Arg1007Lys (c.3020G>A)?

AlphaMissense predicts likely benign (score 0.0756) — an in-silico prediction, not a clinical call.

ADNP p.Arg1007Lys

c.3020G>A · rs2515573849 · VCV2634022

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0756 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ADNP-related disorder

Computational evidence

Protein change
AlphaMissense	0.0756	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -5.37	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.9, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 812 bp · p 0.00064 · regional, not allelic
Overall
CADD	17.54	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

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,038 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,886 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ADNP
Protein: p.Arg1007Lys
Coding: c.3020G>A
MANE Select: NM_001282531
dbSNP: rs2515573849
Type: single nucleotide variant
Location: chr20:50891694 (GRCh38)
Gene constraint: LOEUF 0.106 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.07
Residue 1007: the 'disordered' region

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

Disease context

ADNP-related disorder

Similar variants

ADNP p.Arg1007Gly Uncertain significance ★ ⚠ same residue
ADNP p.Arg306Ter Pathogenic/Likely pathogenic ★★ same condition
ADNP p.Arg730Ter Pathogenic/Likely pathogenic ★★ same condition
ADNP p.Tyr719Ter Pathogenic ★★ same condition
ADNP p.Val343Ala Uncertain significance ★★ ⚠ same condition
ADNP c.-5-1G>T Likely pathogenic ★ same condition
ADNP p.Asn486Ser Likely pathogenic ★ ⚠ same condition
ADNP p.Arg784Gly 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/adnp-p-arg1007lys (accessed [today's date]).

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