PGLS p.Pro182=
c.546G>A · VCV4684338
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.825%, mid)
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 -4.7 | GERP -5.2 |
| Overall | ||
| CADD | 0.259 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.825%
Middle Eastern · 50/6,062 alleles
Filtering AF
0.643%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.578%
Overall
0.0585%
945/1,614,076 alleles · rare
exomes 887/1,461,810 · genomes 58/152,266 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.825% | 121 |
| South Asian | 0.269% | 372 |
| Remaining individualsnot grpmax-eligible | 0.0688% | 1,454 |
| European (non-Finnish) | 0.0467% | 2,142 |
| East Asian | 0.0401% | 2,493 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0372% | 2,692 |
| Admixed American | 0.035% | 2,858 |
| African / African-American | 0.008% | 12,506 |
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
- PGLS
- Protein
- p.Pro182=
- Coding
- c.546G>A
- MANE Select
- NM_012088
- Type
- single nucleotide variant
- Location
- chr19:17517757 (GRCh38)
- Gene constraint
- LOEUF 1.638 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 95.09
Similar variants
- PGLS p.Ala210Val Uncertain significance ★★ ⚠ same type
- PGLS p.Ile171Thr Uncertain significance ★★ ⚠ same type
- PGLS p.Val11Met Uncertain significance ★★ ⚠ same type
- PGLS p.Ala122Val Uncertain significance ★ ⚠ same type
- PGLS p.Ala31Thr Uncertain significance ★ ⚠ same type
- PGLS p.Ala35Val Uncertain significance ★ ⚠ same type
- PGLS p.Ala3Thr Uncertain significance ★ ⚠ same type
- PGLS p.Ala5Thr 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/pgls-p-pro182 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown