ATRIP p.Leu623=
c.1869C>T · VCV3464055
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.004%, afr)
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 -0.09 | GERP -0.95, phastCons 0.3 |
| Overall | ||
| CADD | 5.158 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.004%
African / African-American · 3/74,928 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000495%
Overall
0.000248%
4/1,614,034 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.004% | 24,976 |
| European (non-Finnish) | 8.47e-05% | 1,180,044 |
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
- ATRIP
- Protein
- p.Leu623=
- Coding
- c.1869C>T
- MANE Select
- NM_130384
- Type
- single nucleotide variant
- Location
- chr3:48463868 (GRCh38)
- Gene constraint
- LOEUF 0.707 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.10 · 24 PDB
Similar variants
- ATRIP p.Leu623Ile Uncertain significance ★ ⚠ same residue
- ATRIP p.Leu623Phe Uncertain significance ★ ⚠ same residue
- TREX1 p.Arg114His Pathogenic/Likely pathogenic ★★ ⚠ same type
- TREX1 p.Arg164Ter Pathogenic/Likely pathogenic ★★ same type
- TREX1 p.Asp18Asn Pathogenic ★★ same type
- TREX1 p.Asp200His Likely pathogenic ★★ same type
- TREX1 p.Gln135Ter Pathogenic/Likely pathogenic ★★ same type
- ATRIP p.Ala119Thr 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/atrip-p-leu623 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown