CCDC154 p.Arg347His
c.1040G>A · VCV3486143
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00684%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.012 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.4 | GERP -0.36 |
| Regional constraint | o/e 1.03 | unconstrained · MANE · 9,911 bp · p 0.42 · regional, not allelic |
| Overall | ||
| CADD | 12.64 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00684%
African / African-American · 5/73,068 alleles
Filtering AF
0.0037%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00331%
Overall
0.00421%
65/1,543,144 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00684% | 14,614 |
| Admixed American | 0.00595% | 16,821 |
| European (non-Finnish) | 0.00472% | 21,168 |
| Remaining individualsnot grpmax-eligible | 0.00335% | 29,870 |
| South Asian | 0.0012% | 83,276 |
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.Arg347His
- Coding
- c.1040G>A
- MANE Select
- NM_001143980
- Type
- single nucleotide variant
- Location
- chr16:1438162 (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-arg347his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown