Is DNAH5 p.Ser1764Pro (c.5290T>C) pathogenic?

DNAH5 p.Ser1764Pro (c.5290T>C) is classified Pathogenic/Likely pathogenic in DNAH5 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-05-30). AlphaMissense: likely pathogenic (0.9137); Very rare (popmax 0.00676%, amr); Associated with DNAH5-related disorders.

What condition is associated with DNAH5 p.Ser1764Pro (c.5290T>C)?

DNAH5 p.Ser1764Pro (c.5290T>C) is associated with DNAH5-related disorders, primary ciliary dyskinesia 3, primary ciliary dyskinesia (ClinVar).

How common is DNAH5 p.Ser1764Pro (c.5290T>C) in the general population?

DNAH5 p.Ser1764Pro (c.5290T>C) is very rare (popmax 0.00676%, amr) (gnomAD).

What do computational predictors say about DNAH5 p.Ser1764Pro (c.5290T>C)?

AlphaMissense predicts likely pathogenic (score 0.9137) — an in-silico prediction, not a clinical call.

DNAH5 p.Ser1764Pro

c.5290T>C · rs748763552 · VCV238980

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely pathogenic

0.9137 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00676%, amr)

Conditions

DNAH5-related disorders

Computational evidence

Protein change
AlphaMissense	0.9137	likely pathogenic ✓ concordant with ClinVar
REVEL	0.357	indeterminate
Splicing
SpliceAI	Δ0.44	acceptor loss, 16 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 228 kb · p 0.16 · regional, not allelic
Overall
CADD	24.0	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 0.00676% Admixed American · 4/59,210 alleles

Filtering AF 0.00228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0014%

Overall 0.00212% 33/1,556,108 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00676%	14,802
European (non-Finnish)	0.00239%	41,909
Remaining individualsnot grpmax-eligible	0.00165%	60,518
African / African-American	0.00139%	71,932

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.Ser1764Pro
Coding: c.5290T>C
MANE Select: NM_001369
dbSNP: rs748763552
Type: single nucleotide variant
Location: chr5:13841886 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1764: the 'stem' region

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

Disease context

DNAH5-related disorders

Also linked: primary ciliary dyskinesia 3 primary ciliary dyskinesia

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-ser1764pro (accessed [today's date]).

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