GCM2 p.Pro137=
c.411C>T · rs373057036 · VCV763448
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00668%, eas)
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 -3.5 | GERP -3.9 |
| Overall | ||
| CADD | 5.588 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00668%
East Asian · 3/44,902 alleles
Filtering AF
0.00275%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00244%
Overall
0.00341%
55/1,613,920 alleles · very rare
exomes 53/1,461,730 · genomes 2/152,190 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00668% | 14,967 |
| Admixed American | 0.005% | 20,001 |
| South Asian | 0.00439% | 22,769 |
| European (non-Finnish) | 0.00364% | 27,440 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,480 |
| African / African-American | 0.00133% | 74,916 |
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.Pro137=
- Coding
- c.411C>T
- MANE Select
- NM_004752
- dbSNP
- rs373057036
- Type
- single nucleotide variant
- Location
- chr6:10876490 (GRCh38)
- Gene constraint
- LOEUF 1.205 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 58.78
- Residue 137
- a DNA-binding region; a UniProt-annotated variant site (in fih2; transcription of mrna, but loss of protein expression)
Similar variants
- GCM2 p.Pro137Thr Uncertain significance ★ ⚠ 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-pro137 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown