GCLC p.Pro176=
c.528A>G · rs34307437 · VCV768098
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.31%, afr)
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 -1.7 | GERP -2.1 |
| Overall | ||
| CADD | 4.691 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.31%
African / African-American · 2,483/75,000 alleles
Filtering AF
3.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.16%
Overall
0.174%
2,806/1,613,354 alleles · low-frequency
exomes 1,467/1,461,070 · genomes 1,339/152,284 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.31% | 30 |
| Remaining individualsnot grpmax-eligible | 0.178% | 563 |
| Admixed American | 0.135% | 741 |
| Middle Eastern | 0.132% | 758 |
| South Asian | 0.104% | 959 |
| European (non-Finnish) | 0.00237% | 42,118 |
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
- GCLC
- Protein
- p.Pro176=
- Coding
- c.528A>G
- MANE Select
- NM_001498
- dbSNP
- rs34307437
- Type
- single nucleotide variant
- Location
- chr6:53516141 (GRCh38)
- Gene constraint
- LOEUF 0.404 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 93.68
Similar variants
- GCLC p.Ala511Thr Uncertain significance ★★ ⚠ same type
- GCLC p.Arg287Gln Uncertain significance ★★ ⚠ same type
- GCLC p.Arg312Gln Uncertain significance ★★ ⚠ same type
- GCLC p.Arg66Gln Uncertain significance ★★ ⚠ same type
- GCLC p.Arg66Trp Uncertain significance ★★ ⚠ same type
- GCLC p.Asp351His Uncertain significance ★★ ⚠ same type
- GCLC p.Asp59Glu Uncertain significance ★★ same type
- GCLC p.Gln108Arg 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/gclc-p-pro176 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown