Is DNAH5 p.Ile4450Val (c.13348A>G) pathogenic?

DNAH5 p.Ile4450Val (c.13348A>G) is classified Benign/Likely benign in DNAH5 (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0589); Common (popmax 55.2%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with primary ciliary dyskinesia.

What condition is associated with DNAH5 p.Ile4450Val (c.13348A>G)?

DNAH5 p.Ile4450Val (c.13348A>G) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 3 (ClinVar).

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 DNAH5 p.Ile4450Val (c.13348A>G)?

AlphaMissense predicts likely benign (score 0.0589) — an in-silico prediction, not a clinical call.

DNAH5 p.Ile4450Val

Q: How common is DNAH5 p.Ile4450Val (c.13348A>G) in the general population?

DNAH5 p.Ile4450Val (c.13348A>G) is common (popmax 55.2%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.13348A>G · rs3734110 · VCV163132

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

AlphaMissense

likely benign

0.0589 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 55.2%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.0589	likely benign
REVEL	0.062	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.2	GERP -2, phastCons 0.25
Regional constraint	o/e 0.90	unconstrained · MANE · 25 kb · p 0.038 · regional, not allelic
Overall
CADD	9.497	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 55.2% European (non-Finnish) · 646,132/1,169,808 alleles

Filtering AF 55.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 55.1%

Overall 53.7% 861,079/1,602,296 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	58.9%	2
European (non-Finnish)grpmax	55.2%	2
Middle Eastern	54.3%	2
Ashkenazi Jewishnot grpmax-eligible	54%	2
Remaining individualsnot grpmax-eligible	53%	2
Finnishnot grpmax-eligible	52.9%	2
African / African-American	51.2%	2
Admixed American	51.1%	2
South Asian	45.5%	2
East Asian	41%	2

Amish 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: DNAH5
Protein: p.Ile4450Val
Coding: c.13348A>G
MANE Select: NM_001369
dbSNP: rs3734110
Type: single nucleotide variant
Location: chr5:13701427 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 4450: a UniProt-annotated variant site (in)

Full DNAH5 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

Also linked: primary ciliary dyskinesia 3

For Primary ciliary dyskinesia (Orphanet):

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

Similar variants

DNAH5 c.10555+1G>C Likely pathogenic ★★ same condition
DNAH5 c.1089+1G>A Pathogenic ★★ same condition
DNAH5 c.11028+2T>C Pathogenic/Likely pathogenic ★★ same condition
DNAH5 c.11029-2A>T Pathogenic/Likely pathogenic ★★ same condition
DNAH5 c.11571-1G>A Pathogenic ★★ same condition
DNAH5 c.12910-1G>C Pathogenic/Likely pathogenic ★★ same condition
DNAH5 c.1320+1G>A Likely pathogenic ★★ same condition
DNAH5 c.13338+1G>A 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/dnah5-p-ile4450val (accessed [today's date]).

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