Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 10 submitters
gnomAD v4.1
Common
common (popmax 89.6%, afr) — too common for a highly-penetrant pathogenic allele
Conditions
1
microcephalic osteodysplastic primordial dwarfism type II
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 2.8 | GERP 4.2, phastCons 1 |
| Overall | ||
| CADD | 3.562 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
89.6%
African / African-American · 67,275/75,052 alleles
Filtering AF
89.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 88.8%
Overall
86.9%
1,402,384/1,614,110 alleles · common
exomes 1,270,024/1,461,832 · genomes 132,360/152,278 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 89.6% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 88.7% | 1 |
| European (non-Finnish) | 88% | 1 |
| Remaining individualsnot grpmax-eligible | 86.7% | 1 |
| Finnishnot grpmax-eligible | 84.2% | 1 |
| Middle Eastern | 83.8% | 1 |
| Admixed American | 83.4% | 1 |
| Amishnot grpmax-eligible | 79.3% | 1 |
| South Asian | 79% | 1 |
| East Asian | 78.2% | 1 |
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
- PCNT
- Protein
- p.Leu976=
- Coding
- c.2928C>G
- MANE Select
- NM_006031
- dbSNP
- rs2839228
- Type
- single nucleotide variant
- Location
- chr21:46366902 (GRCh38)
- Gene constraint
- LOEUF 0.943 · pLI <0.01 (gnomAD)
Similar variants
- PCNT c.1032+1G>A Pathogenic/Likely pathogenic ★★ same condition
- PCNT c.1680-1G>C Likely pathogenic ★★ same condition
- PCNT c.5995-2A>C Likely pathogenic ★★ same condition
- PCNT c.7024+1G>C Likely pathogenic ★★ same condition
- PCNT c.7691-1G>A Likely pathogenic ★★ same condition
- PCNT c.9624-2A>G Likely pathogenic ★★ same condition
- PCNT p.Arg1730Ter Pathogenic/Likely pathogenic ★★ same condition
- PCNT p.Arg1923Ter Pathogenic/Likely pathogenic ★★ 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/pcnt-p-leu976 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown