CRLF1 p.Lys149=
c.447G>A · rs114059820 · VCV711726
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.15%, afr)
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 -0.23 | GERP -0.61, phastCons 0.14 |
| Overall | ||
| CADD | 9.112 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.15%
African / African-American · 1,611/74,998 alleles
Filtering AF
2.06%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.03%
Overall
0.114%
1,842/1,614,062 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.15% | 47 |
| Middle Eastern | 0.214% | 466 |
| Admixed American | 0.155% | 645 |
| Remaining individualsnot grpmax-eligible | 0.146% | 687 |
| South Asian | 0.00439% | 22,771 |
| European (non-Finnish) | 0.00254% | 39,333 |
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.Lys149=
- Coding
- c.447G>A
- MANE Select
- NM_004750
- dbSNP
- rs114059820
- Type
- single nucleotide variant
- Location
- chr19:18598852 (GRCh38)
- Gene constraint
- LOEUF 1.045 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.15 · 1 PDB
- Residue 149
- a disulfide bond; the fibronectin type-iii 1 domain
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-lys149 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown