Is DNAAF6 p.Pro63= (c.189T>C) pathogenic?

DNAAF6 p.Pro63= (c.189T>C) is classified Likely benign in DNAAF6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-19). Very rare (popmax 0.0018%, sas).

How common is DNAAF6 p.Pro63= (c.189T>C) in the general population?

DNAAF6 p.Pro63= (c.189T>C) is very rare (popmax 0.0018%, sas) (gnomAD).

DNAAF6 p.Pro63=

c.189T>C · rs1170231450 · VCV2988744

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0018%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.64	GERP -3, phastCons 1
Overall
CADD	8.217	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0018% South Asian · 1/55,635 alleles

Overall 0.000184% 2/1,088,788 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00211%	47,329
South Asiangrpmax	0.0018%	55,635

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro63=
Coding: c.189T>C
MANE Select: NM_173494
dbSNP: rs1170231450
Type: single nucleotide variant
Location: chrX:107216706 (GRCh38)
Structure: AlphaFold pLDDT 73.41
Residue 63: the 'disordered' region; 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)

Full DNAAF6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAAF6 p.Pro63Ser Uncertain significance ★ ⚠ same residue
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

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-pro63 (accessed [today's date]).

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