ASPH p.Ser517=
c.1551C>T · VCV4748706
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0637%, sas)
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 -0.25 | GERP -3.9, phastCons 0.002 |
| Overall | ||
| CADD | 9.975 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0637%
South Asian · 58/91,052 alleles
Filtering AF
0.0505%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0458%
Overall
0.00564%
91/1,613,080 alleles · ultra-rare
exomes 81/1,460,872 · genomes 10/152,208 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0637% | 1,570 |
| East Asian | 0.00892% | 11,211 |
| Remaining individualsnot grpmax-eligible | 0.00801% | 12,489 |
| African / African-American | 0.00667% | 14,998 |
| Admixed American | 0.00167% | 59,996 |
| European (non-Finnish) | 0.00153% | 65,513 |
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
- ASPH
- Protein
- p.Ser517=
- Coding
- c.1551C>T
- MANE Select
- NM_004318
- Type
- single nucleotide variant
- Location
- chr8:61553106 (GRCh38)
- Gene constraint
- LOEUF 1.011 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 72.34 · 43 PDB
Similar variants
- ASPH p.Arg735Trp Likely pathogenic ★★ same type
- ASPH p.Tyr565Ter Pathogenic/Likely pathogenic ★★ same type
- ASPH p.Arg425Cys Uncertain significance ★★ ⚠ same type
- ASPH p.Arg753His Uncertain significance ★★ ⚠ same type
- ASPH p.Glu506Val Uncertain significance ★★ same type
- ASPH p.Leu433Arg Uncertain significance ★★ ⚠ same type
- ASPH p.Ser299Asn Uncertain significance ★★ ⚠ same type
- ASPH p.Val214Met 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/asph-p-ser517 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown