Is ADNP p.Val981= (c.2943G>T) pathogenic?

ADNP p.Val981= (c.2943G>T) is classified Benign/Likely benign in ADNP (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-03). Rare (popmax 0.165%, mid); Associated with ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder.

How common is ADNP p.Val981= (c.2943G>T) in the general population?

ADNP p.Val981= (c.2943G>T) is rare (popmax 0.165%, mid) (gnomAD).

ADNP p.Val981=

Q: What condition is associated with ADNP p.Val981= (c.2943G>T)?

ADNP p.Val981= (c.2943G>T) is associated with ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder (ClinVar).

c.2943G>T · rs143103063 · VCV712654

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.165%, mid)

Conditions

ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder

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 0.23	GERP -3.8, phastCons 0.007
Overall
CADD	1.497	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.165% Middle Eastern · 10/6,062 alleles

Filtering AF 0.153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.151%

Overall 0.132% 2,131/1,614,176 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.165%	606
European (non-Finnish)	0.159%	628
Remaining individualsnot grpmax-eligible	0.134%	744
Admixed American	0.0916%	1,091
Ashkenazi Jewishnot grpmax-eligible	0.0878%	1,139
South Asian	0.0571%	1,752
African / African-American	0.0227%	4,415
Finnishnot grpmax-eligible	0.0109%	9,147

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.Val981=
Coding: c.2943G>T
MANE Select: NM_001282531
dbSNP: rs143103063
Type: single nucleotide variant
Location: chr20:50891771 (GRCh38)
Gene constraint: LOEUF 0.106 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.07
Residue 981: the 'disordered' region

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

Disease context

ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ADNP p.Val981Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
ADNP p.Val981Leu Uncertain significance ★ ⚠ same residue
ADNP p.Val981Met 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

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-val981 (accessed [today's date]).

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