Is ADNP p.Ser889Thr (c.2666G>C) pathogenic?

ADNP p.Ser889Thr (c.2666G>C) is classified Benign/Likely benign in ADNP (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-05-01). AlphaMissense: likely benign (0.068); Low-frequency (popmax 1.3%, afr); Associated with ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder.

How common is ADNP p.Ser889Thr (c.2666G>C) in the general population?

ADNP p.Ser889Thr (c.2666G>C) is low-frequency (popmax 1.3%, afr) (gnomAD).

What do computational predictors say about ADNP p.Ser889Thr (c.2666G>C)?

AlphaMissense predicts likely benign (score 0.068) — an in-silico prediction, not a clinical call.

ADNP p.Ser889Thr

Q: What condition is associated with ADNP p.Ser889Thr (c.2666G>C)?

ADNP p.Ser889Thr (c.2666G>C) is associated with ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder (ClinVar).

c.2666G>C · rs34342624 · VCV588325

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.068 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.3%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.068	likely benign
REVEL	0.159	moderately benign-leaning
SaProt	LLR -7.21	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 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 812 bp · p 0.00064 · regional, not allelic
Overall
CADD	20.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.3% African / African-American · 975/75,046 alleles

Filtering AF 1.23% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.2%

Overall 0.068% 1,098/1,614,180 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.3%	77
Remaining individualsnot grpmax-eligible	0.106%	947
Admixed American	0.075%	1,334
Middle Eastern	0.0495%	2,021
South Asian	0.00878%	11,385
European (non-Finnish)	8.47e-05%	1,180,032

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.Ser889Thr
Coding: c.2666G>C
MANE Select: NM_001282531
dbSNP: rs34342624
Type: single nucleotide variant
Location: chr20:50892048 (GRCh38)
Gene constraint: LOEUF 0.106 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.07
Residue 889: the 'disordered' region; a modified residue (phosphoserine)

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.Ser889fs Likely pathogenic ★ same residue
ADNP p.Ser889Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
ADNP p.Ser889Ile 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-ser889thr (accessed [today's date]).

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