PCNT p.Pro2274=
c.6822G>A · rs375741970 · VCV211875
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.95%, sas)
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 | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.8 | GERP -5.2 |
| Overall | ||
| CADD | 0.36 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.95%
South Asian · 2,648/89,682 alleles
Filtering AF
2.86%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.82%
Overall
0.178%
2,838/1,597,238 alleles · low-frequency
exomes 2,673/1,444,930 · genomes 165/152,308 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 2.95% | 34 |
| Remaining individualsnot grpmax-eligible | 0.159% | 630 |
| Middle Eastern | 0.138% | 725 |
| Admixed American | 0.0118% | 8,457 |
| African / African-American | 0.0107% | 9,352 |
| European (non-Finnish) | 0.00581% | 17,219 |
| East Asian | 0.00224% | 44,644 |
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.Pro2274=
- Coding
- c.6822G>A
- MANE Select
- NM_006031
- dbSNP
- rs375741970
- Type
- single nucleotide variant
- Location
- chr21:46416740 (GRCh38)
- Gene constraint
- LOEUF 0.943 · pLI <0.01 (gnomAD)
- Residue 2274
- a UniProt-annotated variant site (in)
Similar variants
- PCNT p.Pro2274Leu Benign ★★ same residue
- 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
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-pro2274 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown