CRLF1 p.Pro239=
c.717C>T · VCV4800437
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.2 | GERP -2.7 |
| Overall | ||
| CADD | 4.147 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,056 alleles
Filtering AF
0.00138%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00116%
Overall
0.00185%
27/1,460,494 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,056 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00339% | 29,534 |
| European (non-Finnish) | 0.00203% | 49,149 |
| South Asian | 0.0011% | 91,000 |
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
- CRLF1
- Protein
- p.Pro239=
- Coding
- c.717C>T
- MANE Select
- NM_004750
- Type
- single nucleotide variant
- Location
- chr19:18597030 (GRCh38)
- Gene constraint
- LOEUF 1.045 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.15 · 1 PDB
- Residue 239
- the fibronectin type-iii 2 domain
Similar variants
- CRLF1 p.Pro239fs Pathogenic ★★ same residue
- CRLF1 c.397+1G>A Pathogenic/Likely pathogenic ★★ same type
- CRLF1 p.Trp177Ter Pathogenic ★★ same type
- CRLF1 p.Arg119Cys Uncertain significance ★★ same type
- CRLF1 p.Arg81His Uncertain significance ★★ ⚠ same type
- CRLF1 p.Asn168Lys Uncertain significance ★★ ⚠ same type
- CRLF1 p.Asp223Asn Uncertain significance ★★ ⚠ same type
- CRLF1 p.Gly158Ala 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/crlf1-p-pro239 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown