ATAD3A p.Pro496=
c.1488G>A · rs377483917 · VCV2638038
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00593%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.095 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.7 | GERP -2.5 |
| Overall | ||
| CADD | 1.149 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00593%
European (non-Finnish) · 70/1,179,616 alleles
Filtering AF
0.00478%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00439%
Overall
0.00484%
78/1,613,148 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00593% | 16,852 |
| South Asian | 0.0044% | 22,753 |
| Admixed American | 0.00333% | 29,985 |
| African / African-American | 0.00267% | 37,445 |
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
- ATAD3A
- Protein
- p.Pro496=
- Coding
- c.1488G>A
- MANE Select
- NM_001170535
- dbSNP
- rs377483917
- Type
- single nucleotide variant
- Location
- chr1:1527845 (GRCh38)
- Gene constraint
- LOEUF 0.861 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.35
- Residue 496
- a UniProt-annotated variant site (in phrinl)
Similar variants
- ATAD3A p.Pro496Leu Uncertain significance ★★ ⚠ same residue
- ATAD3A c.1266+1G>A Likely pathogenic ★★ same type
- ATAD3A c.384+1G>A Likely pathogenic ★★ same type
- ATAD3A p.Arg528Gln Likely pathogenic ★★ ⚠ same type
- ATAD3A p.Arg528Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
- ATAD3A c.282+5G>A Uncertain significance ★★ same type
- ATAD3A c.283-3C>T Uncertain significance ★★ same type
- ATAD3A c.385-3C>G 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/atad3a-p-pro496 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown