CLCF1 p.Ser8=
c.24G>A · rs141954460 · VCV730799
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.204%, nfe)
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 4 | GERP 1.1, phastCons 1 |
| Overall | ||
| CADD | 14.86 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.204%
European (non-Finnish) · 2,404/1,179,958 alleles
Filtering AF
0.197%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.194%
Overall
0.163%
2,622/1,613,254 alleles · rare
exomes 2,432/1,461,000 · genomes 190/152,254 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.204% | 491 |
| Admixed American | 0.183% | 545 |
| Remaining individualsnot grpmax-eligible | 0.122% | 822 |
| Middle Eastern | 0.0355% | 2,819 |
| African / African-American | 0.0227% | 4,412 |
| East Asian | 0.0112% | 8,968 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,796 |
| South Asian | 0.00659% | 15,173 |
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
- CLCF1
- Protein
- p.Ser8=
- Coding
- c.24G>A
- MANE Select
- NM_013246
- dbSNP
- rs141954460
- Type
- single nucleotide variant
- Location
- chr11:67367619 (GRCh38)
- Gene constraint
- LOEUF 0.734 · pLI 0.33 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 82.59 · 2 PDB
Similar variants
- CLCF1 p.Ser8Leu Uncertain significance ★ same residue
- CLCF1 p.Ser8Pro Uncertain significance ★ ⚠ same residue
- CLCF1 p.Arg122His Uncertain significance ★★ ⚠ same type
- CLCF1 p.Arg130His Uncertain significance ★★ ⚠ same type
- CLCF1 p.Arg30His Uncertain significance ★★ ⚠ same type
- CLCF1 p.Pro38Ser Uncertain significance ★★ ⚠ same type
- CLCF1 p.Ser198Leu Uncertain significance ★★ ⚠ same type
- CLC p.Asn65Lys 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/clcf1-p-ser8 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown