GCM2 p.Pro429=
c.1287C>T · VCV4802342
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 | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.2 | GERP -0.14, phastCons 0.084 |
| Overall | ||
| CADD | 1.927 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.012%
African / African-American · 9/74,938 alleles
Filtering AF
0.00623%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00467%
Overall
0.000558%
9/1,614,076 alleles · ultra-rare
exomes 3/1,461,878 · genomes 6/152,198 · joint denominator
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.Pro429=
- Coding
- c.1287C>T
- MANE Select
- NM_004752
- Type
- single nucleotide variant
- Location
- chr6:10874229 (GRCh38)
- Gene constraint
- LOEUF 1.205 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 58.78
- Residue 429
- a UniProt-annotated variant site (in fih2; transcription of mrna, but loss of protein expression)
Similar variants
- GCM2 p.Pro429Leu 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-pro429 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown