ADNP p.Pro356=
c.1068A>G · VCV4761697
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
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 -3.8 |
| Overall | ||
| CADD | 0.929 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,026 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000248%
4/1,614,210 alleles · very rare
exomes 4/1,461,882 · genomes 0/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,026 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,506 |
| European (non-Finnish) | 0.000169% | 590,016 |
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.Pro356=
- Coding
- c.1068A>G
- MANE Select
- NM_001282531
- Type
- single nucleotide variant
- Location
- chr20:50893646 (GRCh38)
- Gene constraint
- LOEUF 0.106 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 57.07
- Residue 356
- the 'disordered' region; the 'neuroprotective peptide (nap)' region
Similar variants
- ADNP p.Pro356Ser Uncertain significance ★ ⚠ same residue
- ADNP p.Arg173Ter Pathogenic ★★ same type
- ADNP p.Arg216Ter Pathogenic ★★ same type
- ADNP p.Arg225Ter Pathogenic/Likely pathogenic ★★ same type
- ADNP p.Arg306Ter Pathogenic/Likely pathogenic ★★ same type
- ADNP p.Arg730Ter Pathogenic/Likely pathogenic ★★ same type
- ADNP p.Ser738Ter Pathogenic ★★ same type
- ADNP p.Trp446Ter Pathogenic ★★ same type
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-pro356 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown