Is ADNP p.Ser889Arg (c.2667T>A) pathogenic?

ADNP p.Ser889Arg (c.2667T>A) is classified Conflicting classifications of pathogenicity in ADNP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-24). AlphaMissense: likely benign (0.1909); Ultra-rare (popmax 0.033%, mid); Associated with Inborn genetic diseases.

What condition is associated with ADNP p.Ser889Arg (c.2667T>A)?

ADNP p.Ser889Arg (c.2667T>A) is associated with Inborn genetic diseases (ClinVar).

How common is ADNP p.Ser889Arg (c.2667T>A) in the general population?

ADNP p.Ser889Arg (c.2667T>A) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about ADNP p.Ser889Arg (c.2667T>A)?

AlphaMissense predicts likely benign (score 0.1909) — an in-silico prediction, not a clinical call.

ADNP p.Ser889Arg

c.2667T>A · rs750568080 · VCV1794511

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1909 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1909	likely benign
REVEL	0.152	moderately benign-leaning
SaProt	LLR -7.70	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 -1.7	GERP -1.8
Regional constraint	o/e 1.19	unconstrained · MANE · 812 bp · p 0.00064 · regional, not allelic
Overall
CADD	13.12	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 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00919% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00735%

Overall 0.00452% 73/1,614,216 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
South Asian	0.0154%	6,506
European (non-Finnish)	0.00466%	21,455
Admixed American	0.00167%	60,030
Remaining individualsnot grpmax-eligible	0.0016%	62,510

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.Ser889Arg
Coding: c.2667T>A
MANE Select: NM_001282531
dbSNP: rs750568080
Type: single nucleotide variant
Location: chr20:50892047 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ADNP p.Ser889Thr Benign/Likely benign ★★ same residue
ADNP p.Ser889Ile 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-ser889arg (accessed [today's date]).

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