Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 5.04%, afr) — too common for a highly-penetrant pathogenic allele
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 -11 | GERP -3.8 |
| Overall | ||
| CADD | 4.008 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
5.04%
African / African-American · 3,781/75,034 alleles
Filtering AF
4.9%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.85%
Overall
0.264%
4,258/1,613,084 alleles · common
exomes 2,117/1,460,806 · genomes 2,141/152,278 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 5.04% | 20 |
| Remaining individualsnot grpmax-eligible | 0.344% | 291 |
| Admixed American | 0.308% | 324 |
| Middle Eastern | 0.247% | 404 |
| South Asian | 0.0121% | 8,280 |
| European (non-Finnish) | 0.00415% | 24,078 |
| Finnishnot grpmax-eligible | 0.00316% | 31,631 |
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
- PACS2
- Protein
- p.Ser299=
- Coding
- c.897C>T
- MANE Select
- NM_001100913
- dbSNP
- rs4074003
- Type
- single nucleotide variant
- Location
- chr14:105376863 (GRCh38)
- Gene constraint
- LOEUF 0.561 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.10
- Residue 299
- the 'disordered' region
Similar variants
- PACS2 p.Glu209Lys Pathogenic/Likely pathogenic ★★ ⚠ same type
- PACS2 c.1413+2T>C Uncertain significance ★★ same type
- PACS2 p.Ala526Val Uncertain significance ★★ ⚠ same type
- PACS2 p.Ala704Thr Uncertain significance ★★ ⚠ same type
- PACS2 p.Ala883Thr Uncertain significance ★★ ⚠ same type
- PACS2 p.Arg431Gln Uncertain significance ★★ ⚠ same type
- PACS2 p.Arg445Trp Uncertain significance ★★ ⚠ same type
- PACS2 p.Arg514Lys 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/pacs2-p-ser299 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown