PACS2 p.Pro280=
c.840C>T · rs781899422 · VCV1627011
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.182%, sas)
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 -20 | GERP -3.5 |
| Overall | ||
| CADD | 0.474 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.182%
South Asian · 166/91,080 alleles
Filtering AF
0.16%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.151%
Overall
0.0127%
205/1,613,180 alleles · rare
exomes 192/1,460,880 · genomes 13/152,300 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.182% | 549 |
| Middle Eastern | 0.033% | 3,031 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,248 |
| Admixed American | 0.00667% | 15,002 |
| African / African-American | 0.00267% | 37,522 |
| European (non-Finnish) | 0.00178% | 56,185 |
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.Pro280=
- Coding
- c.840C>T
- MANE Select
- NM_001100913
- dbSNP
- rs781899422
- Type
- single nucleotide variant
- Location
- chr14:105376806 (GRCh38)
- Gene constraint
- LOEUF 0.561 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.10
Similar variants
- PACS2 p.Pro280Ser Uncertain significance ★ ⚠ same residue
- 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
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-pro280 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown