ADD1 p.Leu384=
c.1152C>T · rs145251004 · VCV734964
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.115%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.458 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -15 | GERP -3.8 |
| Overall | ||
| CADD | 0.518 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.115%
European (non-Finnish) · 1,354/1,180,012 alleles
Filtering AF
0.11%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.108%
Overall
0.0896%
1,446/1,614,064 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.115% | 871 |
| Remaining individualsnot grpmax-eligible | 0.0784% | 1,276 |
| Admixed American | 0.0267% | 3,750 |
| African / African-American | 0.024% | 4,167 |
| East Asian | 0.00668% | 14,961 |
| Finnishnot grpmax-eligible | 0.00469% | 21,345 |
| South Asian | 0.00329% | 30,351 |
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
- ADD1
- Protein
- p.Leu384=
- Coding
- c.1152C>T
- MANE Select
- NM_001354761
- dbSNP
- rs145251004
- Type
- single nucleotide variant
- Location
- chr4:2899426 (GRCh38)
- Gene constraint
- LOEUF 0.387 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 65.73
Similar variants
- ADD1 p.Val234= Benign ★★ same type
- ADD1 p.Val559Met Benign ★★ same type
- ADD1 c.2047+530G>A Uncertain significance ★ same type
- ADD1 c.2047+541G>T Uncertain significance ★ same type
- ADD1 p.Ala137Val Uncertain significance ★ ⚠ same type
- ADD1 p.Ala151Thr Uncertain significance ★ ⚠ same type
- ADD1 p.Ala156Thr Uncertain significance ★ ⚠ same type
- ADD1 p.Ala18Thr 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/add1-p-leu384 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown