DEF8 p.Pro318=
c.954G>A · rs77908930 · VCV717054
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.64%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.22 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -9.7 | GERP -3.5 |
| Overall | ||
| CADD | 1.896 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.64%
African / African-American · 1,227/75,020 alleles
Filtering AF
1.56%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.53%
Overall
0.091%
1,469/1,613,718 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.64% | 61 |
| Middle Eastern | 0.248% | 403 |
| Admixed American | 0.133% | 750 |
| Remaining individualsnot grpmax-eligible | 0.0848% | 1,179 |
| European (non-Finnish) | 0.00746% | 13,407 |
| East Asian | 0.00669% | 14,944 |
| South Asian | 0.00329% | 30,353 |
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
- DEF8
- Protein
- p.Pro318=
- Coding
- c.954G>A
- MANE Select
- NM_001242818
- dbSNP
- rs77908930
- Type
- single nucleotide variant
- Location
- chr16:89963395 (GRCh38)
- Gene constraint
- LOEUF 0.928 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.04
Similar variants
- DEF8 p.Gln29Glu Benign ★★ same type
- DEF8 p.Glu122= Benign ★★ same type
- DEF8 p.Val356Met Likely benign ★★ ⚠ same type
- DEF8 c.-11+101C>T Uncertain significance ★ ⚠ same type
- DEF8 c.-11+104C>T Uncertain significance ★ ⚠ same type
- DEF8 c.-11+10G>T Uncertain significance ★ ⚠ same type
- DEF8 c.-11+113C>A Uncertain significance ★ ⚠ same type
- DEF8 c.-11+113C>T 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/def8-p-pro318 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown