Is ADNP p.Glu1024Val (c.3071A>T) pathogenic?

ADNP p.Glu1024Val (c.3071A>T) is classified Uncertain significance in ADNP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-09). AlphaMissense: likely benign (0.1974); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with ADNP p.Glu1024Val (c.3071A>T)?

ADNP p.Glu1024Val (c.3071A>T) is associated with Inborn genetic diseases (ClinVar).

How common is ADNP p.Glu1024Val (c.3071A>T) in the general population?

ADNP p.Glu1024Val (c.3071A>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ADNP p.Glu1024Val (c.3071A>T)?

AlphaMissense predicts likely benign (score 0.1974) — an in-silico prediction, not a clinical call.

ADNP p.Glu1024Val

c.3071A>T · rs1980738684 · VCV1912858

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1974 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1974	likely benign
REVEL	0.244	benign-leaning
SaProt	LLR -6.90	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 6.2	GERP 1.9, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 812 bp · p 0.00064 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,914 alleles

Overall 0.000657% 1/152,212 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.Glu1024Val
Coding: c.3071A>T
MANE Select: NM_001282531
dbSNP: rs1980738684
Type: single nucleotide variant
Location: chr20:50891643 (GRCh38)
Gene constraint: LOEUF 0.106 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.07
Residue 1024: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ADNP p.Glu1024Gln Likely benign ★ same residue
ADNP p.Glu1024= Likely benign ★ same residue
ADNP p.Ser738Ter Pathogenic ★★ same condition
ADNP p.Trp446Ter Pathogenic ★★ same condition
ADNP p.Arg264Gln Uncertain significance ★★ ⚠ same condition
ADNP p.Arg296Gln Uncertain significance ★★ ⚠ same condition
ADNP p.Asn331Tyr Uncertain significance ★★ ⚠ same condition
ADNP p.Asn951Ser 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-glu1024val (accessed [today's date]).

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