CCDC8 p.Ala371=
c.1113C>G · rs139601189 · VCV788471
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.79%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.006 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -5.8 | GERP -2.6 |
| Overall | ||
| CADD | 0.452 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.79%
African / African-American · 1,327/74,258 alleles
Filtering AF
1.71%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.67%
Overall
0.092%
1,459/1,586,464 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.79% | 56 |
| Remaining individualsnot grpmax-eligible | 0.108% | 930 |
| Admixed American | 0.0702% | 1,424 |
| Middle Eastern | 0.0167% | 5,976 |
| European (non-Finnish) | 0.00198% | 50,572 |
| South Asian | 0.00115% | 86,822 |
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
- CCDC8
- Protein
- p.Ala371=
- Coding
- c.1113C>G
- MANE Select
- NM_032040
- dbSNP
- rs139601189
- Type
- single nucleotide variant
- Location
- chr19:46411698 (GRCh38)
- Gene constraint
- LOEUF 1.796 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 46.83 · 1 PDB
- Residue 371
- the 'disordered' region
Similar variants
- CCDC8 p.Ala217Thr Uncertain significance ★★ ⚠ same type
- CCDC8 p.Ala293Thr Uncertain significance ★★ ⚠ same type
- CCDC8 p.Ala393Val Uncertain significance ★★ ⚠ same type
- CCDC8 p.Ala527Val Uncertain significance ★★ ⚠ same type
- CCDC8 p.Arg15Gln Uncertain significance ★★ ⚠ same type
- CCDC8 p.Arg225Gly Uncertain significance ★★ ⚠ same type
- CCDC8 p.Arg277His Uncertain significance ★★ ⚠ same type
- CCDC8 p.Arg277Ser 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/ccdc8-p-ala371 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown