CLTCL1 p.Ser1544=
c.4632G>A · VCV4684448
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0439%, sas)
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 -8.5 | GERP -3.4 |
| Overall | ||
| CADD | 0.681 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0439%
South Asian · 40/91,092 alleles
Filtering AF
0.0331%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0293%
Overall
0.00378%
61/1,613,676 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0439% | 2,277 |
| African / African-American | 0.00666% | 15,015 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,622 |
| Admixed American | 0.00334% | 29,982 |
| Finnishnot grpmax-eligible | 0.00157% | 63,712 |
| European (non-Finnish) | 0.000763% | 131,098 |
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
- CLTCL1
- Protein
- p.Ser1544=
- Coding
- c.4632G>A
- MANE Select
- NM_007098
- Type
- single nucleotide variant
- Location
- chr22:19183585 (GRCh38)
- Gene constraint
- LOEUF 0.993 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.53
- Residue 1544
- the 'heavy chain arm' region; the 'proximal segment' region
Similar variants
- CLTCL1 p.Arg1226Cys Uncertain significance ★★ ⚠ same type
- CLTCL1 p.Gln1113Lys Uncertain significance ★★ ⚠ same type
- CLTCL1 p.Gln1142Arg Uncertain significance ★★ ⚠ same type
- CLTCL1 p.Glu1212Lys Uncertain significance ★★ ⚠ same type
- CLTCL1 p.Gly464Arg Uncertain significance ★★ ⚠ same type
- CLTCL1 p.Ser1061Gly Uncertain significance ★★ ⚠ same type
- CLTCL1 p.Ser707Gly Uncertain significance ★★ ⚠ same type
- CLTCL1 p.Val948Gly 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/cltcl1-p-ser1544 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown