Is DNAH5 p.Ser3774Pro (c.11320T>C) pathogenic?

DNAH5 p.Ser3774Pro (c.11320T>C) is classified Conflicting classifications of pathogenicity in DNAH5 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-06). AlphaMissense: ambiguous (0.4958); Ultra-rare (popmax 0.0493%, mid); Associated with primary ciliary dyskinesia 3.

What condition is associated with DNAH5 p.Ser3774Pro (c.11320T>C)?

DNAH5 p.Ser3774Pro (c.11320T>C) is associated with primary ciliary dyskinesia 3, primary ciliary dyskinesia (ClinVar).

How common is DNAH5 p.Ser3774Pro (c.11320T>C) in the general population?

DNAH5 p.Ser3774Pro (c.11320T>C) is ultra-rare (popmax 0.0493%, mid) (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.Ser3774Pro (c.11320T>C)?

AlphaMissense predicts ambiguous (score 0.4958) — an in-silico prediction, not a clinical call.

DNAH5 p.Ser3774Pro

c.11320T>C · rs766646786 · VCV651152

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

ambiguous

0.4958 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Conditions

primary ciliary dyskinesia 3

Computational evidence

Protein change
AlphaMissense	0.4958	ambiguous
REVEL	0.672	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 228 kb · p 0.16 · regional, not allelic
Overall
CADD	23.8	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 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.018% 290/1,613,890 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
Ashkenazi Jewishnot grpmax-eligible	0.0304%	3,289
Remaining individualsnot grpmax-eligible	0.0272%	3,675
European (non-Finnish)	0.0212%	4,720
Admixed American	0.01%	9,996
African / African-American	0.00534%	18,713
South Asian	0.0011%	91,084

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.Ser3774Pro
Coding: c.11320T>C
MANE Select: NM_001369
dbSNP: rs766646786
Type: single nucleotide variant
Location: chr5:13737387 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3774: the 'aaa 5' region

Full DNAH5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary ciliary dyskinesia

For Primary ciliary dyskinesia (Orphanet):

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

Similar variants

DNAH5 p.Ser3774= Conflicting classifications of pathogenicity ★ same residue
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

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-ser3774pro (accessed [today's date]).

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