Is DNAAF3 p.Pro101Ser (c.301C>T) pathogenic?

DNAAF3 p.Pro101Ser (c.301C>T) is classified Uncertain significance in DNAAF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). AlphaMissense: likely benign (0.1409); Ultra-rare (popmax 0.0167%, amr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAAF3 p.Pro101Ser (c.301C>T)?

DNAAF3 p.Pro101Ser (c.301C>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAAF3 p.Pro101Ser (c.301C>T) in the general population?

DNAAF3 p.Pro101Ser (c.301C>T) is ultra-rare (popmax 0.0167%, amr) (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 DNAAF3 p.Pro101Ser (c.301C>T)?

AlphaMissense predicts likely benign (score 0.1409) — an in-silico prediction, not a clinical call.

DNAAF3 p.Pro101Ser

c.301C>T · rs745672775 · VCV1964059

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1409 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.1409	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -9.71	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 7.2	GERP -0.11, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 7,348 bp · p 0.5 · regional, not allelic
Overall
CADD	18.75	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 0.0167% Admixed American · 10/59,990 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.000991% 16/1,614,028 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	5,999
Middle Eastern	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.000339%	295,010

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.Pro101Ser
Coding: c.301C>T
MANE Select: NM_001256715
dbSNP: rs745672775
Type: single nucleotide variant
Location: chr19:55165391 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.06

Full DNAAF3 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

DNAAF3 p.Pro101= Likely benign ★ same residue
DNAAF3 p.Pro101Thr Uncertain significance ★ ⚠ same residue
DNAAF3 c.789+1G>C Likely pathogenic ★★ same condition
DNAAF3 p.Asn252Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
DNAAF3 p.Gln301Ter Pathogenic/Likely pathogenic ★★ same condition
DNAAF3 c.789+5G>C Uncertain significance ★★ same condition
DNAAF3 c.-37G>A Uncertain significance ★★ same condition
DNAAF3 p.Ala128Thr 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/dnaaf3-p-pro101ser (accessed [today's date]).

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