PACS2 p.Ser396=
c.1188C>G · rs782609794 · VCV1937353
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00178%, nfe)
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 -5.2 | GERP -3.2 |
| Overall | ||
| CADD | 4.572 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00178%
European (non-Finnish) · 21/1,179,646 alleles
Filtering AF
0.00114%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000971%
Overall
0.0013%
21/1,612,478 alleles · very rare
exomes 21/1,460,154 · genomes 0/152,324 · joint denominator
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.Ser396=
- Coding
- c.1188C>G
- MANE Select
- NM_001100913
- dbSNP
- rs782609794
- Type
- single nucleotide variant
- Location
- chr14:105381019 (GRCh38)
- Gene constraint
- LOEUF 0.561 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.10
- Residue 396
- the 'disordered' region
Similar variants
- PACS2 p.Ser396_Thr397delinsTrpGly 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-ser396 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown