Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 13 submitters
gnomAD v4.1
Common
common (popmax 80.2%, eas) — too common for a highly-penetrant pathogenic allele
Conditions
1
lysinuric protein intolerance
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 -15 | GERP -4.7 |
| Overall | ||
| CADD | 6.77 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
80.2%
East Asian · 35,992/44,866 alleles
Filtering AF
79.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 79.2%
Overall
60.2%
970,671/1,613,394 alleles · common
exomes 882,157/1,461,424 · genomes 88,514/151,970 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 80.2% | 1 |
| Admixed American | 71.5% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 65.6% | 2 |
| Finnishnot grpmax-eligible | 61.4% | 2 |
| Amishnot grpmax-eligible | 61.4% | 2 |
| Remaining individualsnot grpmax-eligible | 60.4% | 2 |
| European (non-Finnish) | 60.3% | 2 |
| Middle Eastern | 58.3% | 2 |
| South Asian | 48.4% | 2 |
| African / African-American | 47.9% | 2 |
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
- SLC7A7
- Protein
- p.Ser53=
- Coding
- c.159G>A
- MANE Select
- NM_003982
- dbSNP
- rs1805059
- Type
- single nucleotide variant
- Location
- chr14:22813240 (GRCh38)
- Gene constraint
- LOEUF 1.007 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.89 · 6 PDB
- Residue 53
- a UniProt-annotated variant site (in lpi); a β-strand
Disease context
lysinuric protein intolerance — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Lysinuric protein intolerance (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
- Prevalence
- 1-9 / 100 000 (Europe)
Similar variants
- SLC7A7 p.Ser53Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- SLC7A7 p.Ser53Ter Pathogenic ★ same residue
- SLC7A7 c.1429+1G>C Pathogenic ★★ same condition
- SLC7A7 c.625+1G>A Pathogenic ★★ same condition
- SLC7A7 c.625+1G>T Pathogenic/Likely pathogenic ★★ same condition
- SLC7A7 c.770+1G>T Pathogenic/Likely pathogenic ★★ same condition
- SLC7A7 c.894+1G>T Pathogenic/Likely pathogenic ★★ same condition
- SLC7A7 c.895-2A>G Pathogenic ★★ same condition
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/slc7a7-p-ser53 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown