ADNP2 p.Pro704=
c.2112G>A · rs35954328 · VCV2648838
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.439%, nfe)
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 -5.5 | GERP -3.7 |
| Overall | ||
| CADD | 0.462 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.439%
European (non-Finnish) · 5,179/1,180,036 alleles
Filtering AF
0.429%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.425%
Overall
0.351%
5,671/1,614,202 alleles · rare
exomes 5,384/1,461,886 · genomes 287/152,316 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.439% | 228 |
| Remaining individualsnot grpmax-eligible | 0.378% | 265 |
| Admixed American | 0.12% | 834 |
| South Asian | 0.079% | 1,265 |
| Finnishnot grpmax-eligible | 0.0781% | 1,280 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0608% | 1,645 |
| African / African-American | 0.0586% | 1,706 |
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
- ADNP2
- Protein
- p.Pro704=
- Coding
- c.2112G>A
- MANE Select
- NM_014913
- dbSNP
- rs35954328
- Type
- single nucleotide variant
- Location
- chr18:80137525 (GRCh38)
- Gene constraint
- LOEUF 0.896 · pLI 0.18 (gnomAD)
- Structure
- AlphaFold pLDDT 58.42
Similar variants
- ADNP2 p.Gly54Val Uncertain significance ★★ ⚠ same type
- ADNP2 p.Ala222Thr Uncertain significance ★ ⚠ same type
- ADNP2 p.Ala271Val Uncertain significance ★ ⚠ same type
- ADNP2 p.Ala287Thr Uncertain significance ★ ⚠ same type
- ADNP2 p.Ala326Pro Uncertain significance ★ ⚠ same type
- ADNP2 p.Ala451Gly Uncertain significance ★ ⚠ same type
- ADNP2 p.Ala493Ser Uncertain significance ★ ⚠ same type
- ADNP2 p.Ala511Thr Uncertain significance ★ ⚠ 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/adnp2-p-pro704 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown