Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 9 submitters
gnomAD v4.1
Common
common (popmax 41.5%, eas) — 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 -20 | GERP -3.3 |
| Overall | ||
| CADD | 0.005 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
41.5%
East Asian · 18,625/44,876 alleles
Filtering AF
41%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 40.8%
Overall
32.4%
522,504/1,613,610 alleles · common
exomes 477,176/1,461,512 · genomes 45,328/152,098 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 41.5% | 2 |
| Amishnot grpmax-eligible | 38.4% | 3 |
| Middle Eastern | 37.9% | 3 |
| European (non-Finnish) | 33.2% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 32.9% | 3 |
| Remaining individualsnot grpmax-eligible | 32.3% | 3 |
| Finnishnot grpmax-eligible | 31.6% | 3 |
| South Asian | 30.9% | 3 |
| African / African-American | 23.3% | 4 |
| Admixed American | 23% | 4 |
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.Ser514=
- Coding
- c.1542C>A
- MANE Select
- NM_006031
- dbSNP
- rs2249057
- Type
- single nucleotide variant
- Location
- chr21:46353189 (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-ser514 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown