Is DNAH11 p.Asp2425His (c.7273G>C) pathogenic?

DNAH11 p.Asp2425His (c.7273G>C) is classified Conflicting classifications of pathogenicity in DNAH11 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-02-13). AlphaMissense: likely benign (0.175); Very rare (popmax 0.00534%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH11 p.Asp2425His (c.7273G>C)?

DNAH11 p.Asp2425His (c.7273G>C) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH11 p.Asp2425His (c.7273G>C) in the general population?

DNAH11 p.Asp2425His (c.7273G>C) is very rare (popmax 0.00534%, afr) (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 DNAH11 p.Asp2425His (c.7273G>C)?

AlphaMissense predicts likely benign (score 0.175) — an in-silico prediction, not a clinical call.

DNAH11 p.Asp2425His

c.7273G>C · rs374151422 · VCV1385375

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.175 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.175	likely benign
REVEL	0.185	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.63	GERP -2.9
Regional constraint	o/e 1.28	unconstrained · MANE · 358 kb · p 1.1e-96 · regional, not allelic
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,850 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000311% 5/1,610,046 alleles · very rare exomes 3/1,457,972 · genomes 2/152,074 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,713
Admixed American	0.00168%	59,604

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.Asp2425His
Coding: c.7273G>C
MANE Select: NM_001277115
dbSNP: rs374151422
Type: single nucleotide variant
Location: chr7:21725817 (GRCh38)
Gene constraint: LOEUF 0.912 · pLI <0.01 (gnomAD)

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.Asp2425= Likely benign ★ 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-asp2425his (accessed [today's date]).

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