GSC p.Phe57=
c.171C>T · rs933991393 · VCV739656
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00665%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 4.8 | GERP 0.29, phastCons 1 |
| Overall | ||
| CADD | 13.73 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00665%
European (non-Finnish) · 74/1,113,382 alleles
Filtering AF
0.00542%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00496%
Overall
0.00523%
76/1,452,348 alleles · very rare
exomes 65/1,300,310 · genomes 11/152,038 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00665% | 15,046 |
| African / African-American | 0.00298% | 33,586 |
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
- GSC
- Protein
- p.Phe57=
- Coding
- c.171C>T
- MANE Select
- NM_173849
- dbSNP
- rs933991393
- Type
- single nucleotide variant
- Location
- chr14:94769845 (GRCh38)
- Gene constraint
- LOEUF 1.398 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.68 · 1 PDB
Similar variants
- GSC p.Phe57Cys Uncertain significance ★ ⚠ same residue
- GSC p.Ala26Val Uncertain significance ★★ ⚠ same type
- GSC p.Ala30Val Uncertain significance ★★ ⚠ same type
- GSC p.Lys183Gln Uncertain significance ★★ ⚠ same type
- GSC p.Tyr54Ser Uncertain significance ★★ ⚠ same type
- GSC c.356-186C>T Benign ★★ same type
- GSC p.Ala72Thr Benign ★★ same type
- GSC p.Asn140= Benign/Likely benign ★★ 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/gsc-p-phe57 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown