APRT p.Leu177=
c.529C>T · rs565636938 · VCV744458
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.255%, sas)
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 · G>C here scores Δ0.27 · evaluated, not missing |
|---|---|---|
| Pangolin | Δ0.22 | gain · loss 0.00 · SpliceAI below 0.2 · independent |
| Constraint at this position | ||
| Conservation | phyloP 2.5 | GERP 0.45, phastCons 1 |
| Overall | ||
| CADD | 8.497 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.255%
South Asian · 232/91,086 alleles
Filtering AF
0.228%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.217%
Overall
0.0174%
281/1,613,414 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.255% | 393 |
| Middle Eastern | 0.0495% | 2,021 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,499 |
| European (non-Finnish) | 0.00347% | 28,781 |
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
- APRT
- Protein
- p.Leu177=
- Coding
- c.529C>T
- MANE Select
- NM_000485
- dbSNP
- rs565636938
- Type
- single nucleotide variant
- Location
- chr16:88809712 (GRCh38)
- Gene constraint
- LOEUF 1.789 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.91 · 16 PDB
- Residue 177
- a β-strand
Similar variants
- APRT p.Arg67Gln Likely pathogenic ★★ same type
- APRT p.Arg67Ter Pathogenic ★★ same type
- APRT p.Arg87Ter Pathogenic ★★ same type
- APRT p.Asp65Val Pathogenic ★★ same type
- APRT p.Gly133Arg Likely pathogenic ★★ same type
- APRT p.Gly63Asp Likely pathogenic ★★ same type
- APRT p.Met1Ile Pathogenic ★★ same type
- APRT p.Met1Val Pathogenic ★★ 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/aprt-p-leu177 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown