Is DNAAF6 p.Thr151Arg (c.452C>G) pathogenic?

DNAAF6 p.Thr151Arg (c.452C>G) is classified Uncertain significance in DNAAF6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-14). AlphaMissense: ambiguous (0.5488); Very rare (popmax 0.000335%, nfe).

How common is DNAAF6 p.Thr151Arg (c.452C>G) in the general population?

DNAAF6 p.Thr151Arg (c.452C>G) is very rare (popmax 0.000335%, nfe) (gnomAD).

What do computational predictors say about DNAAF6 p.Thr151Arg (c.452C>G)?

AlphaMissense predicts ambiguous (score 0.5488) — an in-silico prediction, not a clinical call.

DNAAF6 p.Thr151Arg

c.452C>G · VCV4697592

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5488 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000335%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5488	ambiguous
REVEL	0.157	moderately benign-leaning
SaProt	LLR -14.37	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP 1.6, phastCons 0.74
Regional constraint	o/e 0.86	unconstrained · MANE · 30 kb · p 0.087 · regional, not allelic
Overall
CADD	23.3	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 0.000335% European (non-Finnish) · 3/894,674 alleles

Filtering AF 8.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000248% 3/1,208,621 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: DNAAF6
Protein: p.Thr151Arg
Coding: c.452C>G
MANE Select: NM_173494
Type: single nucleotide variant
Location: chrX:107238944 (GRCh38)
Structure: AlphaFold pLDDT 73.41
Residue 151: 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); a UniProt-annotated variant site (in cild36; almost complete loss of inner dynein arms and less loss of outer dynein arms in motor cilia; immotile cilia; abolishes interaction with dnai2); a UniProt-annotated variant site (in cild36; defective preassembly of outer and inner dynein arms)

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

Similar variants

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
DNAAF6 c.153+10T>C Likely benign ★★ 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-thr151arg (accessed [today's date]).

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