CRLF1 p.Pro333=
c.999C>A · rs766994193 · VCV2881938
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>C here scores Δ0.24 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.3 | GERP -3, phastCons 1 |
| Overall | ||
| CADD | 8.483 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,014 alleles
Overall
0.000124%
2/1,613,886 alleles · very rare
exomes 2/1,461,558 · genomes 0/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,014 |
| European (non-Finnish) | 8.47e-05% | 1,179,954 |
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.Pro333=
- Coding
- c.999C>A
- MANE Select
- NM_004750
- dbSNP
- rs766994193
- Type
- single nucleotide variant
- Location
- chr19:18596647 (GRCh38)
- Gene constraint
- LOEUF 1.045 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.15 · 1 PDB
- Residue 333
- the fibronectin type-iii 2 domain; the 'disordered' region
Similar variants
- 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
- CRLF1 p.Gly161Arg 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-pro333 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown