Is DNAAF4 p.Lys41= (c.123G>A) pathogenic?

DNAAF4 p.Lys41= (c.123G>A) is classified Uncertain significance in DNAAF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-24). Very rare (popmax 0.00627%, nfe); Associated with primary ciliary dyskinesia.

What condition is associated with DNAAF4 p.Lys41= (c.123G>A)?

DNAAF4 p.Lys41= (c.123G>A) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAAF4 p.Lys41= (c.123G>A) in the general population?

DNAAF4 p.Lys41= (c.123G>A) is very rare (popmax 0.00627%, nfe) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DNAAF4 p.Lys41=

c.123G>A · rs201530487 · VCV643227

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00627%, nfe)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.31 · evaluated, not missing
Pangolin	Δ0.24	loss · gain 0.01 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 7.5	GERP 2.6, phastCons 1
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00627% European (non-Finnish) · 74/1,179,970 alleles

Filtering AF 0.00511% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00651% 105/1,613,884 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0304%	3,288
Finnishnot grpmax-eligible	0.0172%	5,820
European (non-Finnish)grpmax	0.00627%	15,946
East Asian	0.00223%	44,866

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: DNAAF4
Protein: p.Lys41=
Coding: c.123G>A
MANE Select: NM_130810
dbSNP: rs201530487
Type: single nucleotide variant
Location: chr15:55498207 (GRCh38)
Gene constraint: LOEUF 1.018 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.00
Residue 41: the cs domain; the 'mediates interaction with esr1 and stub1' region

Full DNAAF4 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

DNAAF4 p.Arg330Trp Pathogenic/Likely pathogenic ★★ same condition
DNAAF4 p.Pro2Ser Uncertain significance ★★ ⚠ same condition
DNAAF4 p.Ile175fs Pathogenic/Likely pathogenic ★★ same condition
DNAAF4 p.Ser131_Val132insTer Pathogenic/Likely pathogenic ★★ same condition
DNAAF4 c.1048-149_*1048del Pathogenic ★ same condition
DNAAF4 c.784-?_893+?del Pathogenic ★ same condition
DNAAF4 c.1047+1G>A Pathogenic/Likely pathogenic ★★ same type
DNAAF4 c.1153+1G>A Pathogenic ★★ 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/dnaaf4-p-lys41 (accessed [today's date]).

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