Is DNAH2 p.Arg442= (c.1326C>T) pathogenic?

DNAH2 p.Arg442= (c.1326C>T) is classified Likely benign in DNAH2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-17). Ultra-rare (popmax 0.0684%, amr); Associated with DNAH2-related disorder.

What condition is associated with DNAH2 p.Arg442= (c.1326C>T)?

DNAH2 p.Arg442= (c.1326C>T) is associated with DNAH2-related disorder (ClinVar).

How common is DNAH2 p.Arg442= (c.1326C>T) in the general population?

DNAH2 p.Arg442= (c.1326C>T) is ultra-rare (popmax 0.0684%, amr) (gnomAD).

DNAH2 p.Arg442=

c.1326C>T · rs566718536 · VCV3040842

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0684%, amr)

Conditions

DNAH2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.8
Overall
CADD	0.007	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0684% Admixed American · 41/59,970 alleles

Filtering AF 0.0518% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0459%

Overall 0.00378% 61/1,613,916 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0684%	1,463
African / African-American	0.00667%	14,991
Remaining individualsnot grpmax-eligible	0.0016%	62,502
European (non-Finnish)	0.00119%	84,283

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.Arg442=
Coding: c.1326C>T
MANE Select: NM_020877
dbSNP: rs566718536
Type: single nucleotide variant
Location: chr17:7739888 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI <0.01 (gnomAD)
Residue 442: the 'stem' region

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

Disease context

DNAH2-related disorder

Similar variants

DNAH2 p.Arg442His 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-arg442 (accessed [today's date]).

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