Is DNAAF2 p.Pro357Leu (c.1070C>T) pathogenic?

DNAAF2 p.Pro357Leu (c.1070C>T) is classified Uncertain significance in DNAAF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.1093); Very rare (popmax 0.0012%, sas); Associated with primary ciliary dyskinesia 10.

What condition is associated with DNAAF2 p.Pro357Leu (c.1070C>T)?

DNAAF2 p.Pro357Leu (c.1070C>T) is associated with primary ciliary dyskinesia 10 (ClinVar).

How common is DNAAF2 p.Pro357Leu (c.1070C>T) in the general population?

DNAAF2 p.Pro357Leu (c.1070C>T) is very rare (popmax 0.0012%, 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.Pro357Leu (c.1070C>T)?

AlphaMissense predicts likely benign (score 0.1093) — an in-silico prediction, not a clinical call.

DNAAF2 p.Pro357Leu

c.1070C>T · rs1389972313 · VCV880925

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1093 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0012%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia 10

Computational evidence

Protein change
AlphaMissense	0.1093	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -8.54	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 0.082	GERP -0.01, phastCons 0.021
Regional constraint	o/e 1.11	unconstrained · MANE · 9,604 bp · p 0.00019 · regional, not allelic
Overall
CADD	8.877	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0012% South Asian · 1/83,504 alleles

Overall 0.000144% 2/1,385,960 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0012%	83,504
European (non-Finnish)	8.74e-05%	1,143,512

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.Pro357Leu
Coding: c.1070C>T
MANE Select: NM_018139
dbSNP: rs1389972313
Type: single nucleotide variant
Location: chr14:49634080 (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 10 — 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.Pro357Ala Uncertain significance ★★ ⚠ same residue
DNAAF2 p.Gln504Ter Pathogenic/Likely pathogenic ★★ same condition
DNAAF2 p.Glu243Ter Likely pathogenic ★★ same condition
DNAAF2 p.Arg111Pro Uncertain significance ★★ ⚠ same condition
DNAAF2 p.Arg22Gln Uncertain significance ★★ ⚠ same condition
DNAAF2 p.Arg260Leu Uncertain significance ★★ ⚠ same condition
DNAAF2 p.Arg542Trp Uncertain significance ★★ ⚠ same condition
DNAAF2 p.Arg609Gly 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-pro357leu (accessed [today's date]).

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