CCDC154 p.Pro54Leu
c.161C>T · rs925240020 · VCV2227297
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0277%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.013 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.31 | acceptor gain · deltas |
| Pangolin | Δ0.21 | gain · loss 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -0.42 | GERP -2.6 |
| Regional constraint | o/e 1.03 | unconstrained · MANE · 9,911 bp · p 0.42 · regional, not allelic |
| Overall | ||
| CADD | 0.671 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0277%
East Asian · 5/18,046 alleles
Filtering AF
0.0109%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00704%
Overall
0.00207%
27/1,304,194 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0277% | 3,609 |
| Finnishnot grpmax-eligible | 0.00528% | 18,935 |
| South Asian | 0.00494% | 20,260 |
| Admixed American | 0.00459% | 21,781 |
| Remaining individualsnot grpmax-eligible | 0.00457% | 21,862 |
| European (non-Finnish) | 0.00121% | 82,418 |
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
- CCDC154
- Protein
- p.Pro54Leu
- Coding
- c.161C>T
- MANE Select
- NM_001143980
- dbSNP
- rs925240020
- Type
- single nucleotide variant
- Location
- chr16:1443859 (GRCh38)
- Gene constraint
- LOEUF 1.366 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.92
Similar variants
- CCDC154 p.Ala128Val Uncertain significance ★ same type
- CCDC154 p.Ala129Gly Uncertain significance ★ same type
- CCDC154 p.Ala136Val Uncertain significance ★ same type
- CCDC154 p.Ala148Gly Uncertain significance ★ same type
- CCDC154 p.Ala14Thr Uncertain significance ★ same type
- CCDC154 p.Ala177Val Uncertain significance ★ same type
- CCDC154 p.Ala205Val Uncertain significance ★ same type
- CCDC154 p.Ala315Val 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/ccdc154-p-pro54leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown