CHL1 p.Phe700=
c.2100C>T · rs61753583 · VCV729796
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.523%, 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 1.7 | GERP 1.1, phastCons 0.93 |
| Overall | ||
| CADD | 17.07 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.523%
African / African-American · 392/75,000 alleles
Filtering AF
0.48%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.463%
Overall
0.0281%
454/1,613,920 alleles · rare
exomes 235/1,461,704 · genomes 219/152,216 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.523% | 191 |
| Admixed American | 0.04% | 2,499 |
| Remaining individualsnot grpmax-eligible | 0.0256% | 3,906 |
| Middle Eastern | 0.0165% | 6,062 |
| European (non-Finnish) | 0.00178% | 56,186 |
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
- CHL1
- Protein
- p.Phe700=
- Coding
- c.2100C>T
- MANE Select
- NM_006614
- dbSNP
- rs61753583
- Type
- single nucleotide variant
- Location
- chr3:382595 (GRCh38)
- Gene constraint
- LOEUF 0.678 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.37
- Residue 700
- the fibronectin type-iii 1 domain; the 'disordered' region
Similar variants
- CHL1 p.Ile100Val Uncertain significance ★★ ⚠ same type
- CHL1 c.1306+10C>T Benign ★★ same type
- CHL1 c.197+10G>C Benign ★★ same type
- CHL1 p.Ala1105Val Likely benign ★★ same type
- CHL1 p.Ala450= Likely benign ★★ same type
- CHL1 p.Ala465= Benign ★★ same type
- CHL1 p.Arg93= Benign/Likely benign ★★ same type
- CHL1 p.Gln216= 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/chl1-p-phe700 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown