CLCF1 p.Pro36=
c.108T>A · VCV4683644
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 13.6%, afr) — too common for a highly-penetrant pathogenic allele
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 -0.44 | GERP -2.6 |
| Overall | ||
| CADD | 5.815 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
13.6%
African / African-American · 10,171/75,036 alleles
Filtering AF
13.3%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 13.2%
Overall
4.02%
64,927/1,614,136 alleles · common
exomes 55,082/1,461,856 · genomes 9,845/152,280 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 13.6% | 7 |
| East Asian | 10.8% | 9 |
| Middle Eastern | 4.62% | 22 |
| Finnishnot grpmax-eligible | 4.59% | 22 |
| Remaining individualsnot grpmax-eligible | 4.42% | 23 |
| Admixed American | 4.36% | 23 |
| Amishnot grpmax-eligible | 3.73% | 27 |
| European (non-Finnish) | 3.26% | 31 |
| Ashkenazi Jewishnot grpmax-eligible | 2.79% | 36 |
| South Asian | 2.21% | 45 |
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.Pro36=
- Coding
- c.108T>A
- MANE Select
- NM_013246
- Type
- single nucleotide variant
- Location
- chr11:67367535 (GRCh38)
- Gene constraint
- LOEUF 0.734 · pLI 0.33 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 82.59 · 2 PDB
- Residue 36
- an α-helix
Similar variants
- 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
- CLCF1 c.183+14G>A Benign ★★ same type
- CLCF1 p.Arg30Cys Likely 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-pro36 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown