Is DNAH11 p.Leu1663= (c.4987C>T) pathogenic?

DNAH11 p.Leu1663= (c.4987C>T) is classified Likely benign in DNAH11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-08). Ultra-rare (popmax 0.0317%, amr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH11 p.Leu1663= (c.4987C>T)?

DNAH11 p.Leu1663= (c.4987C>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH11 p.Leu1663= (c.4987C>T) in the general population?

DNAH11 p.Leu1663= (c.4987C>T) is ultra-rare (popmax 0.0317%, amr) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

DNAH11 p.Leu1663=

c.4987C>T · rs541180386 · VCV1132075

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0317%, amr)

Conditions

primary ciliary dyskinesia

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 1.1	GERP 0.93, phastCons 0.56
Overall
CADD	7.649	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0317% Admixed American · 19/59,914 alleles

Filtering AF 0.0207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0172%

Overall 0.00155% 25/1,613,346 alleles · ultra-rare exomes 11/1,461,082 · genomes 14/152,264 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0317%	3,153
Remaining individualsnot grpmax-eligible	0.0064%	15,616
African / African-American	0.00133%	75,008
European (non-Finnish)	8.48e-05%	1,179,569

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: DNAH11
Protein: p.Leu1663=
Coding: c.4987C>T
MANE Select: NM_001277115
dbSNP: rs541180386
Type: single nucleotide variant
Location: chr7:21655874 (GRCh38)
Gene constraint: LOEUF 0.912 · pLI <0.01 (gnomAD)
Residue 1663: the 'stem' region

Full DNAH11 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

DNAH11 p.Leu1663Val Conflicting classifications of pathogenicity ★ ⚠ same residue
DNAH11 c.10166-1G>C Likely pathogenic ★★ same condition
DNAH11 c.10569-2A>G Likely pathogenic ★★ same condition
DNAH11 c.10691+1G>T Pathogenic/Likely pathogenic ★★ same condition
DNAH11 c.10896+1G>T Pathogenic/Likely pathogenic ★★ same condition
DNAH11 c.11203-1G>C Pathogenic/Likely pathogenic ★★ same condition
DNAH11 c.11839+1G>A Pathogenic/Likely pathogenic ★★ same condition
DNAH11 c.12934-1G>T Pathogenic/Likely pathogenic ★★ 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/dnah11-p-leu1663 (accessed [today's date]).

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