CCDC154 p.Arg641Gln
c.1922G>A · rs565271689 · VCV3138557
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0507%, mid)
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 -0.43 | GERP -2.5 |
| Regional constraint | o/e 1.03 | unconstrained · MANE · 9,911 bp · p 0.42 · regional, not allelic |
| Overall | ||
| CADD | 7.344 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0507%
Middle Eastern · 3/5,914 alleles
Filtering AF
0.0187%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0158%
Overall
0.00465%
72/1,549,876 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0507% | 1,971 |
| South Asian | 0.0274% | 3,654 |
| African / African-American | 0.00683% | 14,632 |
| Remaining individualsnot grpmax-eligible | 0.00666% | 15,017 |
| East Asian | 0.00489% | 20,459 |
| European (non-Finnish) | 0.00296% | 33,730 |
| Admixed American | 0.00196% | 50,996 |
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.Arg641Gln
- Coding
- c.1922G>A
- MANE Select
- NM_001143980
- dbSNP
- rs565271689
- Type
- single nucleotide variant
- Location
- chr16:1434490 (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-arg641gln (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown