PRG4 p.Pro749=
c.2247C>T · VCV4924148
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0172%, 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 -8.3 | GERP -1.1 |
| Overall | ||
| CADD | 0.777 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0172%
Middle Eastern · 1/5,810 alleles
Filtering AF
0.00596%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00432%
Overall
0.00274%
43/1,568,624 alleles · ultra-rare
exomes 23/1,438,774 · genomes 20/129,850 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0172% | 5,810 |
| African / African-American | 0.012% | 8,308 |
| South Asian | 0.00557% | 17,944 |
| Admixed American | 0.00536% | 18,657 |
| Finnishnot grpmax-eligible | 0.00502% | 19,903 |
| East Asian | 0.00235% | 42,494 |
| European (non-Finnish) | 0.0019% | 52,686 |
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
- PRG4
- Protein
- p.Pro749=
- Coding
- c.2247C>T
- MANE Select
- NM_005807
- Type
- single nucleotide variant
- Location
- chr1:186307966 (GRCh38)
- Gene constraint
- LOEUF 0.801 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 48.76
- Residue 749
- the 'disordered' region; the '59 x 8 aa repeats of k-x-p-x-p-t-t-x' region
Similar variants
- PRG4 p.Arg1166Ter Pathogenic/Likely pathogenic ★★ same type
- PRG4 p.Ser1355Ter Pathogenic/Likely pathogenic ★★ same type
- PRG4 p.Ala1246Val Uncertain significance ★★ ⚠ same type
- PRG4 p.Asp87Asn Uncertain significance ★★ ⚠ same type
- PRG4 p.Lys287Arg Uncertain significance ★★ ⚠ same type
- PRG4 p.Pro409Leu Uncertain significance ★★ ⚠ same type
- PRG4 p.Val1399Phe Uncertain significance ★★ ⚠ same type
- PRG4 c.-30-30T>A 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/prg4-p-pro749 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown