Is DNAH2 p.Arg4389= (c.13165C>A) pathogenic?

DNAH2 p.Arg4389= (c.13165C>A) is classified Benign in DNAH2 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2019-05-01). Low-frequency (popmax 1.8%, afr); Associated with DNAH2-related disorder.

What condition is associated with DNAH2 p.Arg4389= (c.13165C>A)?

DNAH2 p.Arg4389= (c.13165C>A) is associated with DNAH2-related disorder (ClinVar).

How common is DNAH2 p.Arg4389= (c.13165C>A) in the general population?

DNAH2 p.Arg4389= (c.13165C>A) is low-frequency (popmax 1.8%, afr) (gnomAD).

DNAH2 p.Arg4389=

c.13165C>A · rs9904115 · VCV3056665

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.8%, afr)

Conditions

DNAH2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.52	acceptor gain · deltas
Pangolin	Δ0.24	gain · loss 0.17 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.9	GERP -1.4, phastCons 1
Overall
CADD	19.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.8% African / African-American · 1,350/75,042 alleles

Filtering AF 1.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.69%

Overall 0.0923% 1,490/1,614,168 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.8%	56
Remaining individualsnot grpmax-eligible	0.109%	919
Admixed American	0.08%	1,251
Middle Eastern	0.0165%	6,062
South Asian	0.0022%	45,544
European (non-Finnish)	0.00178%	56,192

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: DNAH2
Protein: p.Arg4389=
Coding: c.13165C>A
MANE Select: NM_020877
dbSNP: rs9904115
Type: single nucleotide variant
Location: chr17:7833414 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI <0.01 (gnomAD)
Residue 4389: a UniProt-annotated variant site (in spgf45; decreased protein abundance; loss of inner dynein arm assembly; in spermatozoa from patients)

Full DNAH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DNAH2-related disorder

Similar variants

DNAH2 p.Arg4389Pro Uncertain significance ★ same residue
DNAH2 p.Arg1633Gly Uncertain significance ⚠ same condition
DNAH2 c.11478+4G>A Benign same condition
DNAH2 c.1171-715G>A Likely benign same condition
DNAH2 c.1377-9C>A Likely benign same condition
DNAH2 c.1904+123T>C Benign same condition
DNAH2 c.1904+136C>T Likely benign same condition
DNAH2 c.1904+345A>G Likely benign 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/dnah2-p-arg4389 (accessed [today's date]).

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