Is DNAH5 p.Arg577Thr (c.1730G>C) pathogenic?

DNAH5 p.Arg577Thr (c.1730G>C) is classified Pathogenic/Likely pathogenic in DNAH5 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-12-26). AlphaMissense: likely benign (0.1323); Very rare (popmax 0.00482%, nfe); Associated with Respiratory ciliopathies including non-CF bronchiectasis.

What condition is associated with DNAH5 p.Arg577Thr (c.1730G>C)?

DNAH5 p.Arg577Thr (c.1730G>C) is associated with Respiratory ciliopathies including non-CF bronchiectasis, primary ciliary dyskinesia 3, primary ciliary dyskinesia (ClinVar).

How common is DNAH5 p.Arg577Thr (c.1730G>C) in the general population?

DNAH5 p.Arg577Thr (c.1730G>C) is very rare (popmax 0.00482%, nfe) (gnomAD).

What do computational predictors say about DNAH5 p.Arg577Thr (c.1730G>C)?

AlphaMissense predicts likely benign (score 0.1323) — an in-silico prediction, not a clinical call.

DNAH5 p.Arg577Thr

c.1730G>C · rs397515541 · VCV65637

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.1323 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00482%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Respiratory ciliopathies including non-CF bronchiectasis

Computational evidence

Protein change
AlphaMissense	0.1323	likely benign ⚠ discordant with ClinVar
REVEL	0.141	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	Δ0.89	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.73	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 228 kb · p 0.16 · regional, not allelic
Overall
CADD	25.2	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 0.00482% European (non-Finnish) · 56/1,160,972 alleles

Filtering AF 0.00381% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00342%

Overall 0.00359% 57/1,587,338 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00482%	20,732
Remaining individualsnot grpmax-eligible	0.00163%	61,450

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.Arg577Thr
Coding: c.1730G>C
MANE Select: NM_001369
dbSNP: rs397515541
Type: single nucleotide variant
Location: chr5:13902053 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 577: the 'stem' region

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

Disease context

Respiratory ciliopathies including non-CF bronchiectasis

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-arg577thr (accessed [today's date]).

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