DNAAF3 p.Pro354=
c.1062G>C · rs372843454 · VCV2650514
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00406%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.03 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.22 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -4.2 | GERP -2.1 |
| Overall | ||
| CADD | 6.934 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00406%
East Asian · 1/24,650 alleles
Filtering AF
0.000118%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 8e-05%
Overall
0.000516%
5/969,252 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00406% | 24,650 |
| European (non-Finnish) | 0.000505% | 197,930 |
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
- DNAAF3
- Protein
- p.Pro354=
- Coding
- c.1062G>C
- MANE Select
- NM_001256715
- dbSNP
- rs372843454
- Type
- single nucleotide variant
- Location
- chr19:55160000 (GRCh38)
- Gene constraint
- LOEUF 1.139 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.06
Similar variants
- DNAAF3 p.Pro354Leu Uncertain significance ★ ⚠ same residue
- DNAAF3 c.789+1G>C Likely pathogenic ★★ same type
- DNAAF3 p.Asn252Ser Pathogenic/Likely pathogenic ★★ ⚠ same type
- DNAAF3 p.Gln301Ter Pathogenic/Likely pathogenic ★★ same type
- DNAAF3 c.789+5G>C Uncertain significance ★★ same type
- DNAAF3 c.-37G>A Uncertain significance ★★ same type
- DNAAF3 p.Ala128Thr Uncertain significance ★★ ⚠ same type
- DNAAF3 p.Ala256Gly 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/dnaaf3-p-pro354 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown