PACS2 p.Ser604=
c.1812C>T · rs149063451 · VCV1600135
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0583%, amr)
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 -7.7 | GERP -3.8 |
| Overall | ||
| CADD | 10.41 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0583%
Admixed American · 35/60,006 alleles
Filtering AF
0.0431%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0378%
Overall
0.0303%
488/1,612,142 alleles · ultra-rare
exomes 450/1,459,794 · genomes 38/152,348 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0583% | 1,714 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0406% | 2,466 |
| European (non-Finnish) | 0.0345% | 2,898 |
| Remaining individualsnot grpmax-eligible | 0.0288% | 3,471 |
| Middle Eastern | 0.0165% | 6,062 |
| African / African-American | 0.00799% | 12,510 |
| South Asian | 0.00769% | 13,010 |
| East Asian | 0.00446% | 22,431 |
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.Ser604=
- Coding
- c.1812C>T
- MANE Select
- NM_001100913
- dbSNP
- rs149063451
- Type
- single nucleotide variant
- Location
- chr14:105384384 (GRCh38)
- Gene constraint
- LOEUF 0.561 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.10
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-ser604 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown