GCLC p.Arg296=
c.888C>T · rs368832845 · VCV793593
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0275%, 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 6.6 | GERP -0.034, phastCons 1 |
| Overall | ||
| CADD | 13.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0275%
European (non-Finnish) · 325/1,179,794 alleles
Filtering AF
0.025%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.024%
Overall
0.0216%
348/1,613,690 alleles · ultra-rare
exomes 331/1,461,612 · genomes 17/152,078 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0275% | 3,630 |
| Remaining individualsnot grpmax-eligible | 0.0224% | 4,462 |
| Finnishnot grpmax-eligible | 0.00781% | 12,802 |
| African / African-American | 0.00534% | 18,714 |
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.Arg296=
- Coding
- c.888C>T
- MANE Select
- NM_001498
- dbSNP
- rs368832845
- Type
- single nucleotide variant
- Location
- chr6:53508652 (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-arg296 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown