CCDC154 p.Arg352Gln
c.1055G>A · VCV3486144
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0114%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.016 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.2 | GERP -0.95, phastCons 0.27 |
| Regional constraint | o/e 1.03 | unconstrained · MANE · 9,911 bp · p 0.42 · regional, not allelic |
| Overall | ||
| CADD | 7.742 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0114%
European (non-Finnish) · 131/1,144,832 alleles
Filtering AF
0.00982%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00923%
Overall
0.00938%
145/1,546,414 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0114% | 8,739 |
| Remaining individualsnot grpmax-eligible | 0.00835% | 11,980 |
| Finnishnot grpmax-eligible | 0.00519% | 19,280 |
| Admixed American | 0.00394% | 25,385 |
| African / African-American | 0.00274% | 36,492 |
| South Asian | 0.00239% | 41,903 |
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.Arg352Gln
- Coding
- c.1055G>A
- MANE Select
- NM_001143980
- Type
- single nucleotide variant
- Location
- chr16:1438147 (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-arg352gln (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown