Is ADNP p.Ala1093= (c.3279C>T) pathogenic?

ADNP p.Ala1093= (c.3279C>T) is classified Benign/Likely benign in ADNP (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-03). Rare (popmax 0.23%, nfe); Associated with ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder.

How common is ADNP p.Ala1093= (c.3279C>T) in the general population?

ADNP p.Ala1093= (c.3279C>T) is rare (popmax 0.23%, nfe) (gnomAD).

ADNP p.Ala1093=

Q: What condition is associated with ADNP p.Ala1093= (c.3279C>T)?

ADNP p.Ala1093= (c.3279C>T) is associated with ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder (ClinVar).

c.3279C>T · rs142247083 · VCV434090

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.23%, nfe)

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 -5.2	GERP -3.5
Overall
CADD	0.377	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.23% European (non-Finnish) · 2,714/1,179,262 alleles

Filtering AF 0.223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.22%

Overall 0.179% 2,891/1,610,974 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.23%	435
Remaining individualsnot grpmax-eligible	0.114%	879
African / African-American	0.0507%	1,971
Admixed American	0.0501%	1,996
South Asian	0.0264%	3,782
Finnishnot grpmax-eligible	0.0208%	4,802
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,486

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.Ala1093=
Coding: c.3279C>T
MANE Select: NM_001282531
dbSNP: rs142247083
Type: single nucleotide variant
Location: chr20:50891435 (GRCh38)
Gene constraint: LOEUF 0.106 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.07
Residue 1093: 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.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
ADNP p.Tyr378Ter Pathogenic ★★ same condition
ADNP p.Tyr719Ter 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-ala1093 (accessed [today's date]).

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