CCDC141 p.Arg1463Ser
c.4389G>T · rs866780379 · VCV3138429
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0309%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.118 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.27 | GERP -3.5, phastCons 0.99 |
| Regional constraint | o/e 1.06 | unconstrained · MANE · 216 kb · p 0.0073 · regional, not allelic |
| Overall | ||
| CADD | 17.17 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0309%
South Asian · 26/84,062 alleles
Filtering AF
0.0217%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0185%
Overall
0.00228%
35/1,536,240 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0309% | 3,233 |
| Remaining individualsnot grpmax-eligible | 0.0133% | 7,516 |
| European (non-Finnish) | 8.72e-05% | 1,146,898 |
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
- CCDC141
- Protein
- p.Arg1463Ser
- Coding
- c.4389G>T
- MANE Select
- NM_173648
- dbSNP
- rs866780379
- Type
- single nucleotide variant
- Location
- chr2:178834377 (GRCh38)
- Gene constraint
- LOEUF 1.052 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.36
- Residue 1463
- the ig-like domain
Similar variants
- CCDC141 p.Ala1261Val Uncertain significance ★★ same type
- CCDC141 p.Ala88Thr Uncertain significance ★★ same type
- CCDC141 p.Arg1346Trp Uncertain significance ★★ same type
- CCDC141 p.Arg1482Trp Uncertain significance ★★ same type
- CCDC141 p.Arg180Trp Uncertain significance ★★ same type
- CCDC141 p.Arg287Gln Uncertain significance ★★ same type
- CCDC141 p.Arg468Gln Uncertain significance ★★ same type
- CCDC141 p.Arg891Trp 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/ccdc141-p-arg1463ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown