Is ADNP p.Val856= (c.2568C>T) pathogenic?

ADNP p.Val856= (c.2568C>T) is classified Benign in ADNP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Common (popmax 29.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with ADNP p.Val856= (c.2568C>T)?

ADNP p.Val856= (c.2568C>T) is associated with Inborn genetic diseases, ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder (ClinVar).

ADNP p.Val856=

Q: How common is ADNP p.Val856= (c.2568C>T) in the general population?

ADNP p.Val856= (c.2568C>T) is common (popmax 29.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2568C>T · rs1062651 · VCV587839

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 29.9%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP -0.24, phastCons 1
Overall
CADD	2.238	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 29.9% African / African-American · 22,411/74,922 alleles

Filtering AF 29.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 29.4%

Overall 2.94% 47,517/1,613,998 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	29.9%	3
Remaining individualsnot grpmax-eligible	3.78%	26
Admixed American	3.1%	32
Middle Eastern	3%	33
South Asian	2.79%	36
Ashkenazi Jewishnot grpmax-eligible	1.89%	53
East Asian	1.49%	67
European (non-Finnish)	1.37%	73
Finnishnot grpmax-eligible	1.27%	79

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.Val856=
Coding: c.2568C>T
MANE Select: NM_001282531
dbSNP: rs1062651
Type: single nucleotide variant
Location: chr20:50892146 (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

Also linked: ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder

Similar variants

ADNP p.Val856Asp Uncertain significance ★ ⚠ same residue
ADNP p.Val856Gly Uncertain significance ★ ⚠ same residue
ADNP p.Arg173Ter Pathogenic ★★ same condition
ADNP p.Arg225Ter Pathogenic/Likely pathogenic ★★ same condition
ADNP p.Arg730Ter Pathogenic/Likely pathogenic ★★ same condition
ADNP p.Ser738Ter Pathogenic ★★ same condition
ADNP p.Trp446Ter Pathogenic ★★ same condition
ADNP p.Tyr172Ter Likely 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-val856 (accessed [today's date]).

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