Is DNAH2 p.Arg1046= (c.3138C>T) pathogenic?

DNAH2 p.Arg1046= (c.3138C>T) is classified Benign in DNAH2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-08-11). Low-frequency (popmax 2.28%, eas); Associated with DNAH2-related disorder.

What condition is associated with DNAH2 p.Arg1046= (c.3138C>T)?

DNAH2 p.Arg1046= (c.3138C>T) is associated with DNAH2-related disorder (ClinVar).

How common is DNAH2 p.Arg1046= (c.3138C>T) in the general population?

DNAH2 p.Arg1046= (c.3138C>T) is low-frequency (popmax 2.28%, eas) (gnomAD).

DNAH2 p.Arg1046=

c.3138C>T · rs79442311 · VCV3033376

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 2.28%, eas)

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 -0.42	GERP -2.2, phastCons 0.008
Overall
CADD	6.292	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.28% East Asian · 1,024/44,876 alleles

Filtering AF 2.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.12%

Overall 0.0991% 1,599/1,614,210 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	2.28%	44
Remaining individualsnot grpmax-eligible	0.299%	334
Middle Eastern	0.099%	1,010
Finnishnot grpmax-eligible	0.0609%	1,642
South Asian	0.0362%	2,760
European (non-Finnish)	0.0255%	3,920
Admixed American	0.015%	6,670

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.Arg1046=
Coding: c.3138C>T
MANE Select: NM_020877
dbSNP: rs79442311
Type: single nucleotide variant
Location: chr17:7763990 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI <0.01 (gnomAD)
Residue 1046: 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.Arg1046Cys 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-arg1046 (accessed [today's date]).

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