Is DNAAF5 p.Val261Ile (c.781G>A) pathogenic?

DNAAF5 p.Val261Ile (c.781G>A) is classified Conflicting classifications of pathogenicity in DNAAF5 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-27). AlphaMissense: ambiguous (0.4515); Rare (popmax 0.148%, mid); Associated with primary ciliary dyskinesia 18.

What condition is associated with DNAAF5 p.Val261Ile (c.781G>A)?

DNAAF5 p.Val261Ile (c.781G>A) is associated with primary ciliary dyskinesia 18, primary ciliary dyskinesia (ClinVar).

How common is DNAAF5 p.Val261Ile (c.781G>A) in the general population?

DNAAF5 p.Val261Ile (c.781G>A) is rare (popmax 0.148%, mid) (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 DNAAF5 p.Val261Ile (c.781G>A)?

AlphaMissense predicts ambiguous (score 0.4515) — an in-silico prediction, not a clinical call.

DNAAF5 p.Val261Ile

c.781G>A · rs138915052 · VCV525340

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

ambiguous

0.4515 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.148%, mid)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

primary ciliary dyskinesia 18

Computational evidence

Protein change
AlphaMissense	0.4515	ambiguous
REVEL	0.645	pathogenic-leaning
SaProt	LLR -11.36	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 59 kb · p 0.0084 · regional, not allelic
Overall
CADD	27.3	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 0.148% Middle Eastern · 9/6,062 alleles

Filtering AF 0.0823% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0806%

Overall 0.0785% 1,266/1,613,680 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.294%	340
Middle Easterngrpmax	0.148%	674
Remaining individualsnot grpmax-eligible	0.088%	1,136
European (non-Finnish)	0.0868%	1,152
South Asian	0.0571%	1,751
Admixed American	0.0333%	3,002
African / African-American	0.0147%	6,824
Finnishnot grpmax-eligible	0.0126%	7,941

Ashkenazi Jewish 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: DNAAF5
Protein: p.Val261Ile
Coding: c.781G>A
MANE Select: NM_017802
dbSNP: rs138915052
Type: single nucleotide variant
Location: chr7:740819 (GRCh38)
Gene constraint: LOEUF 1.12 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.80

Full DNAAF5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 18 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary ciliary dyskinesia

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

DNAAF5 c.1470+1G>A Likely pathogenic ★★ same condition
DNAAF5 c.1615-2A>G Likely pathogenic ★★ same condition
DNAAF5 p.Arg253Ter Pathogenic/Likely pathogenic ★★ same condition
DNAAF5 p.Cys500Phe Pathogenic/Likely pathogenic ★★ ⚠ same condition
DNAAF5 p.Leu795Pro Pathogenic/Likely pathogenic ★★ same condition
DNAAF5 p.Trp309Ter Pathogenic/Likely pathogenic ★★ same condition
DNAAF5 c.780+6T>A Uncertain significance ★★ same condition
DNAAF5 c.905+4C>T 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/dnaaf5-p-val261ile (accessed [today's date]).

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