CLTC p.Gln925=
c.2775A>G · rs74649914 · VCV1164679
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.02%, 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 0.34 | GERP -1.1, phastCons 0.97 |
| Overall | ||
| CADD | 7.806 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.02%
African / African-American · 769/75,036 alleles
Filtering AF
0.965%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.941%
Overall
0.0565%
912/1,613,746 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.02% | 98 |
| Middle Eastern | 0.116% | 865 |
| Remaining individualsnot grpmax-eligible | 0.072% | 1,389 |
| Admixed American | 0.0633% | 1,579 |
| South Asian | 0.00878% | 11,385 |
| European (non-Finnish) | 0.00381% | 26,215 |
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
- CLTC
- Protein
- p.Gln925=
- Coding
- c.2775A>G
- MANE Select
- NM_004859
- dbSNP
- rs74649914
- Type
- single nucleotide variant
- Location
- chr17:59677167 (GRCh38)
- Gene constraint
- LOEUF 0.104 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.62 · 10 PDB
- Residue 925
- the 'heavy chain arm' region; the 'proximal segment' region
Similar variants
- CLTC p.Gln925His Uncertain significance ★ ⚠ same residue
- CLTC p.Arg1165Ter Likely pathogenic ★★ same type
- CLTC p.Arg1251Ter Pathogenic/Likely pathogenic ★★ same type
- CLTC p.Arg1311Ter Likely pathogenic ★★ same type
- CLTC p.Arg63Ter Pathogenic ★★ same type
- CLTC p.Pro890Leu Pathogenic/Likely pathogenic ★★ same type
- CLTC p.Tyr1574Ter Pathogenic/Likely pathogenic ★★ same type
- CLTC p.Tyr803Ter Pathogenic/Likely pathogenic ★★ 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/cltc-p-gln925 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown