Is DNAAF2 p.Ser7Phe (c.20C>T) pathogenic?

DNAAF2 p.Ser7Phe (c.20C>T) is classified Conflicting classifications of pathogenicity in DNAAF2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-22). AlphaMissense: likely benign (0.1814); Rare (popmax 0.534%, sas); Associated with primary ciliary dyskinesia.

What condition is associated with DNAAF2 p.Ser7Phe (c.20C>T)?

DNAAF2 p.Ser7Phe (c.20C>T) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 10 (ClinVar).

How common is DNAAF2 p.Ser7Phe (c.20C>T) in the general population?

DNAAF2 p.Ser7Phe (c.20C>T) is rare (popmax 0.534%, sas) (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.Ser7Phe (c.20C>T)?

AlphaMissense predicts likely benign (score 0.1814) — an in-silico prediction, not a clinical call.

DNAAF2 p.Ser7Phe

c.20C>T · rs577796590 · VCV216704

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1814 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.534%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.1814	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -7.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.7, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 9,604 bp · p 0.00019 · regional, not allelic
Overall
CADD	23.1	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 0.534% South Asian · 453/84,886 alleles

Filtering AF 0.493% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.477%

Overall 0.0332% 518/1,562,184 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.534%	187
Middle Eastern	0.252%	397
Remaining individualsnot grpmax-eligible	0.0363%	2,752
Admixed American	0.00572%	17,489
European (non-Finnish)	0.00208%	48,078
African / African-American	0.00136%	73,716

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.Ser7Phe
Coding: c.20C>T
MANE Select: NM_018139
dbSNP: rs577796590
Type: single nucleotide variant
Location: chr14:49635130 (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

Also linked: primary ciliary dyskinesia 10

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.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
DNAAF2 p.Ala211Thr Uncertain significance ★★ ⚠ same condition
DNAAF2 p.Ala358Thr 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-ser7phe (accessed [today's date]).

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