GCM2 p.Asp43=
c.129C>T · VCV3609661
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.012%, 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 -6.1 | GERP -3.6 |
| Overall | ||
| CADD | 0.377 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.012%
African / African-American · 9/74,926 alleles
Filtering AF
0.00623%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00468%
Overall
0.00155%
25/1,614,020 alleles · ultra-rare
exomes 21/1,461,854 · genomes 4/152,166 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.012% | 8,325 |
| South Asian | 0.00439% | 22,770 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,243 |
| East Asian | 0.00223% | 44,890 |
| Admixed American | 0.00167% | 59,988 |
| European (non-Finnish) | 0.000678% | 147,502 |
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
- GCM2
- Protein
- p.Asp43=
- Coding
- c.129C>T
- MANE Select
- NM_004752
- Type
- single nucleotide variant
- Location
- chr6:10877354 (GRCh38)
- Gene constraint
- LOEUF 1.205 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 58.78
- Residue 43
- a DNA-binding region
Similar variants
- GCM2 p.Asp43Glu Likely benign ★★ same residue
- GCM2 c.90+2T>G Likely pathogenic ★★ same type
- GCM2 p.Arg47Leu Pathogenic ★★ same type
- GCM2 p.Arg67Cys Likely pathogenic ★★ same type
- GCM2 p.Tyr136Ter Pathogenic ★★ same type
- GCM2 c.*217T>A Uncertain significance ★★ same type
- GCM2 p.Ala148Val Uncertain significance ★★ ⚠ same type
- GCM2 p.Ala180Pro 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/gcm2-p-asp43 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown