PLAT p.Ser456=
c.1368T>C · VCV4683335
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 18.2%, sas) — 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. | ||
| REVEL | 0.191 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.5 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 7.872 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
18.2%
South Asian · 16,500/90,444 alleles
Filtering AF
18%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 17.9%
Overall
12.3%
198,114/1,607,232 alleles · common
exomes 182,601/1,454,970 · genomes 15,513/152,262 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 18.2% | 5 |
| Finnishnot grpmax-eligible | 17.2% | 6 |
| East Asian | 16.9% | 6 |
| Middle Eastern | 16.7% | 6 |
| Remaining individualsnot grpmax-eligible | 12.9% | 8 |
| Ashkenazi Jewishnot grpmax-eligible | 12.5% | 8 |
| European (non-Finnish) | 12.3% | 8 |
| Amishnot grpmax-eligible | 10.4% | 10 |
| Admixed American | 6.11% | 16 |
| African / African-American | 2.75% | 36 |
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
- PLAT
- Protein
- p.Ser456=
- Coding
- c.1368T>C
- MANE Select
- NM_000930
- Type
- single nucleotide variant
- Location
- chr8:42179059 (GRCh38)
- Gene constraint
- LOEUF 0.804 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.28 · 11 PDB
- Residue 456
- the peptidase s1 domain
Similar variants
- PLAT p.Arg184Gly Uncertain significance ★★ ⚠ same type
- PLAT p.Val280Met Uncertain significance ★★ ⚠ same type
- PLAT p.Ala34Asp Likely benign ★★ same type
- PLAT p.Ala493= Benign/Likely benign ★★ same type
- PLAT p.Arg561Ter Benign ★★ same type
- PLAT p.Pro543= Likely benign ★★ same type
- PLAT p.Ser154= Likely benign ★★ same type
- PLAT p.Ser513= Benign ★★ 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/plat-p-ser456 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown