Is DNAAF2 p.Val20Asp (c.59T>A) pathogenic?

DNAAF2 p.Val20Asp (c.59T>A) is classified Uncertain significance in DNAAF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-11). AlphaMissense: likely pathogenic (0.8404); Very rare (popmax 0.000429%, nfe); Associated with primary ciliary dyskinesia.

What condition is associated with DNAAF2 p.Val20Asp (c.59T>A)?

DNAAF2 p.Val20Asp (c.59T>A) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAAF2 p.Val20Asp (c.59T>A) in the general population?

DNAAF2 p.Val20Asp (c.59T>A) is very rare (popmax 0.000429%, nfe) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DNAAF2 p.Val20Asp (c.59T>A)?

AlphaMissense predicts likely pathogenic (score 0.8404) — an in-silico prediction, not a clinical call.

DNAAF2 p.Val20Asp

c.59T>A · rs1566513874 · VCV580461

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8404 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000429%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.8404	likely pathogenic · top 8% in DNAAF2
REVEL	0.247	benign-leaning
SaProt	LLR -12.62	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 1.7, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 9,604 bp · p 0.00019 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000429% European (non-Finnish) · 5/1,164,926 alleles

Filtering AF 0.000126% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.00035% 5/1,429,546 alleles · very rare

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: DNAAF2
Protein: p.Val20Asp
Coding: c.59T>A
MANE Select: NM_018139
dbSNP: rs1566513874
Type: single nucleotide variant
Location: chr14:49635091 (GRCh38)
Gene constraint: LOEUF 1.811 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.57

Full DNAAF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

DNAAF2 p.Val20Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
DNAAF2 p.Val20= Likely benign ★ same residue
DNAAF2 p.Gln504Ter Pathogenic/Likely pathogenic ★★ same condition
DNAAF2 p.Gln529Ter Pathogenic/Likely pathogenic ★★ same condition
DNAAF2 p.Glu130Ter Pathogenic/Likely pathogenic ★★ same condition
DNAAF2 p.Glu243Ter Likely pathogenic ★★ same condition
DNAAF2 p.Ala100Gly Uncertain significance ★★ ⚠ same condition
DNAAF2 p.Ala126Val Uncertain significance ★★ ⚠ same condition

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/dnaaf2-p-val20asp (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown