GCLC p.Pro233=
c.699G>A · rs758688011 · VCV2994600
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00549%, sas)
Conditions
1
Inborn genetic diseases
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 -6.6 | GERP -3.8 |
| Overall | ||
| CADD | 3.965 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00549%
South Asian · 5/91,058 alleles
Filtering AF
0.00211%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00136%
Overall
0.00105%
17/1,612,914 alleles · very rare
exomes 14/1,460,740 · genomes 3/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00549% | 18,212 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,592 |
| East Asian | 0.00223% | 44,864 |
| Admixed American | 0.00167% | 60,014 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,438 |
| African / African-American | 0.00134% | 74,898 |
| European (non-Finnish) | 0.000594% | 168,434 |
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.Pro233=
- Coding
- c.699G>A
- MANE Select
- NM_001498
- dbSNP
- rs758688011
- Type
- single nucleotide variant
- Location
- chr6:53514258 (GRCh38)
- Gene constraint
- LOEUF 0.404 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 93.68
Similar variants
- GCLC p.Arg287Gln Uncertain significance ★★ ⚠ same condition
- GCLC p.Asp351His Uncertain significance ★★ ⚠ same condition
- GCLC p.Gln108Arg Uncertain significance ★★ ⚠ same condition
- GCLC p.Glu356Lys Uncertain significance ★★ ⚠ same condition
- GCLC p.Gly154Glu Uncertain significance ★★ ⚠ same condition
- GCLC p.Ile350Val Uncertain significance ★★ ⚠ same condition
- GCLC p.Lys625Arg Uncertain significance ★★ ⚠ same condition
- GCLC p.Phe208Ile Uncertain significance ★★ ⚠ same condition
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-pro233 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown