Is ADNP p.Arg296Gln (c.887G>A) pathogenic?

ADNP p.Arg296Gln (c.887G>A) is classified Uncertain significance in ADNP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-11). AlphaMissense: ambiguous (0.4113); Very rare (popmax 0.00329%, sas); Associated with Inborn genetic diseases.

What condition is associated with ADNP p.Arg296Gln (c.887G>A)?

ADNP p.Arg296Gln (c.887G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ADNP p.Arg296Gln (c.887G>A) in the general population?

ADNP p.Arg296Gln (c.887G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about ADNP p.Arg296Gln (c.887G>A)?

AlphaMissense predicts ambiguous (score 0.4113) — an in-silico prediction, not a clinical call.

ADNP p.Arg296Gln

c.887G>A · rs767858345 · VCV1764962

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4113 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4113	ambiguous
REVEL	0.144	moderately benign-leaning
SaProt	LLR -5.99	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.71, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 536 bp · p 0.077 · regional, not allelic
Overall
CADD	25.3	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 0.00329% South Asian · 3/91,084 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00041% 6/1,461,890 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,361
Admixed American	0.00167%	60,016
Finnishnot grpmax-eligible	0.00156%	64,026
European (non-Finnish)	8.47e-05%	1,180,008

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.Arg296Gln
Coding: c.887G>A
MANE Select: NM_001282531
dbSNP: rs767858345
Type: single nucleotide variant
Location: chr20:50893827 (GRCh38)
Gene constraint: LOEUF 0.106 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.07

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.Arg296Trp 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.Asn331Tyr Uncertain significance ★★ ⚠ same condition
ADNP p.Asn951Ser Uncertain significance ★★ ⚠ same condition
ADNP p.Gln302His Uncertain significance ★★ ⚠ same condition
ADNP p.Glu1024Val 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-arg296gln (accessed [today's date]).

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