Is DNAH1 p.Pro283Ser (c.847C>T) pathogenic?

DNAH1 p.Pro283Ser (c.847C>T) is classified Uncertain significance in DNAH1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-05). AlphaMissense: likely pathogenic (0.6925); Very rare (popmax 0.005%, nfe); Associated with ciliary dyskinesia, primary, 37.

What condition is associated with DNAH1 p.Pro283Ser (c.847C>T)?

DNAH1 p.Pro283Ser (c.847C>T) is associated with ciliary dyskinesia, primary, 37, spermatogenic failure 18 (ClinVar).

How common is DNAH1 p.Pro283Ser (c.847C>T) in the general population?

DNAH1 p.Pro283Ser (c.847C>T) is very rare (popmax 0.005%, nfe) (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 DNAH1 p.Pro283Ser (c.847C>T)?

AlphaMissense predicts likely pathogenic (score 0.6925) — an in-silico prediction, not a clinical call.

DNAH1 p.Pro283Ser

c.847C>T · rs371481904 · VCV544606

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6925 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

ciliary dyskinesia, primary, 37

Computational evidence

Protein change
AlphaMissense	0.6925	likely pathogenic
REVEL	0.166	moderately benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.8, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 30 kb · p 0.21 · regional, not allelic
Overall
CADD	20.9	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 0.005% European (non-Finnish) · 59/1,179,822 alleles

Filtering AF 0.00394% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00361%

Overall 0.00384% 62/1,613,778 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.005%	19,997
Remaining individualsnot grpmax-eligible	0.0048%	20,820

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: DNAH1
Protein: p.Pro283Ser
Coding: c.847C>T
MANE Select: NM_015512
dbSNP: rs371481904
Type: single nucleotide variant
Location: chr3:52327990 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Residue 283: the 'stem' region

Full DNAH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ciliary dyskinesia, primary, 37 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: spermatogenic failure 18

For Primary ciliary dyskinesia (Orphanet):

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

Similar variants

DNAH1 c.1034-2A>G Likely pathogenic ★★ same condition
DNAH1 c.10474+1G>A Pathogenic/Likely pathogenic ★★ same condition
DNAH1 c.10968+2C>T Likely pathogenic ★★ same condition
DNAH1 c.5244+1G>A Likely pathogenic ★★ same condition
DNAH1 p.Arg1702Ter Pathogenic ★★ same condition
DNAH1 p.Arg2479Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH1 p.Arg2622Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH1 p.Arg2724Ter 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/dnah1-p-pro283ser (accessed [today's date]).

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