Is DNAH5 p.Ile2018Thr (c.6053T>C) pathogenic?

DNAH5 p.Ile2018Thr (c.6053T>C) is classified Conflicting classifications of pathogenicity in DNAH5 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-07-21). AlphaMissense: likely pathogenic (0.8912); Rare (popmax 0.287%, eas); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH5 p.Ile2018Thr (c.6053T>C)?

DNAH5 p.Ile2018Thr (c.6053T>C) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 3 (ClinVar).

How common is DNAH5 p.Ile2018Thr (c.6053T>C) in the general population?

DNAH5 p.Ile2018Thr (c.6053T>C) is rare (popmax 0.287%, eas) (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 DNAH5 p.Ile2018Thr (c.6053T>C)?

AlphaMissense predicts likely pathogenic (score 0.8912) — an in-silico prediction, not a clinical call.

DNAH5 p.Ile2018Thr

c.6053T>C · rs117989731 · VCV905154

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8912 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.287%, eas)

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.8912	likely pathogenic
REVEL	0.776	moderately pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 228 kb · p 0.16 · regional, not allelic
Overall
CADD	25.4	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 0.287% East Asian · 129/44,882 alleles

Filtering AF 0.247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.232%

Overall 0.00824% 133/1,614,194 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.287%	348
Remaining individualsnot grpmax-eligible	0.0064%	15,625

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.Ile2018Thr
Coding: c.6053T>C
MANE Select: NM_001369
dbSNP: rs117989731
Type: single nucleotide variant
Location: chr5:13830605 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2018: the 'aaa 1' region

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-ile2018thr (accessed [today's date]).

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