DNAAF6 p.Glu141=
c.423A>G · rs759265594 · VCV2964749
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00898%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.21 | donor loss · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.62 | GERP -2.8, phastCons 0.28 |
| Overall | ||
| CADD | 1.065 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00898%
Admixed American · 4/44,553 alleles
Filtering AF
0.00299%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00197%
Overall
0.00304%
33/1,086,043 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00898% | 11,138 |
| European (non-Finnish) | 0.00326% | 30,706 |
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
- DNAAF6
- Protein
- p.Glu141=
- Coding
- c.423A>G
- MANE Select
- NM_173494
- dbSNP
- rs759265594
- Type
- single nucleotide variant
- Location
- chrX:107222835 (GRCh38)
- Structure
- AlphaFold pLDDT 73.41
- Residue 141
- a UniProt-annotated variant site (in cild36; strongly decreased expression at protein level; almost complete loss of outer dynein arms and less loss of inner dynein arms in motor cilia; decreased cilia movement; no effect on trans-golgi network location; abolishes interaction with dnai2); a UniProt-annotated variant site (in cild36; almost complete loss of inner dynein arms and less loss of outer dynein arms in motor cilia; immotile cilia; abolishes interaction with dnai2); a UniProt-annotated variant site (in cild36; defective preassembly of outer and inner dynein arms)
Similar variants
- DNAAF6 c.227-1G>A Pathogenic/Likely pathogenic ★★ same type
- DNAAF6 p.Arg168Cys Uncertain significance ★★ ⚠ same type
- DNAAF6 p.Glu42Gly Uncertain significance ★★ ⚠ same type
- DNAAF6 p.Ile114Phe Uncertain significance ★★ ⚠ same type
- DNAAF6 p.Ile158Val Uncertain significance ★★ ⚠ same type
- DNAAF6 p.Ile192Asn Uncertain significance ★★ ⚠ same type
- DNAAF6 p.Ser18Phe Uncertain significance ★★ ⚠ same type
- DNAAF6 c.153+10T>C Likely benign ★★ 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/dnaaf6-p-glu141 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown