Is ADNP p.Val856Asp (c.2567T>A) pathogenic?

ADNP p.Val856Asp (c.2567T>A) is classified Uncertain significance in ADNP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.2458); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ADNP p.Val856Asp (c.2567T>A)?

ADNP p.Val856Asp (c.2567T>A) is associated with Inborn genetic diseases (ClinVar).

How common is ADNP p.Val856Asp (c.2567T>A) in the general population?

ADNP p.Val856Asp (c.2567T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADNP p.Val856Asp (c.2567T>A)?

AlphaMissense predicts likely benign (score 0.2458) — an in-silico prediction, not a clinical call.

ADNP p.Val856Asp

c.2567T>A · VCV4244606

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2458 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2458	likely benign
REVEL	0.256	benign-leaning
SaProt	LLR -5.73	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 11	GERP 1.8, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 812 bp · p 0.00064 · regional, not allelic
Overall
CADD	22.2	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

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.Val856Asp
Coding: c.2567T>A
MANE Select: NM_001282531
Type: single nucleotide variant
Location: chr20:50892147 (GRCh38)
Gene constraint: LOEUF 0.106 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.07
Residue 856: 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.Val856= Benign ★★ same residue
ADNP p.Val856Gly Uncertain significance ★ ⚠ 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-val856asp (accessed [today's date]).

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