ATAD3B p.Val259=
c.777C>T · rs766091128 · VCV2638016
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0442%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.23 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -10 | GERP -2.9 |
| Overall | ||
| CADD | 0.765 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0442%
African / African-American · 33/74,596 alleles
Filtering AF
0.0323%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0282%
Overall
0.0111%
178/1,601,526 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0442% | 2,260 |
| Middle Eastern | 0.0421% | 2,376 |
| East Asian | 0.0342% | 2,927 |
| Admixed American | 0.0291% | 3,438 |
| South Asian | 0.0202% | 4,956 |
| Remaining individualsnot grpmax-eligible | 0.0129% | 7,735 |
| Finnishnot grpmax-eligible | 0.00973% | 10,280 |
| European (non-Finnish) | 0.00671% | 14,895 |
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
- ATAD3B
- Protein
- p.Val259=
- Coding
- c.777C>T
- MANE Select
- NM_031921
- dbSNP
- rs766091128
- Type
- single nucleotide variant
- Location
- chr1:1485042 (GRCh38)
- Gene constraint
- LOEUF 1.152 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.69
Similar variants
- ATAD3B p.Val259Phe Uncertain significance ★ ⚠ same residue
- ATAD3B c.445-11C>G Benign ★★ same type
- ATAD3B p.Ala71Ser Benign ★★ same type
- ATAD3B p.Cys641= Benign ★★ same type
- ATAD3B p.Phe274Tyr Benign/Likely benign ★★ same type
- ATAD3B p.Pro639Ser Benign ★★ same type
- ATAD3B c.1090-3C>T Uncertain significance ★ same type
- ATAD3B c.325C>T 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/atad3b-p-val259 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown