Is DNAH2 p.Arg3426Gln (c.10277G>A) pathogenic?

DNAH2 p.Arg3426Gln (c.10277G>A) is classified Uncertain significance in DNAH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-03). AlphaMissense: likely benign (0.0888); Ultra-rare (popmax 0.0378%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DNAH2 p.Arg3426Gln (c.10277G>A)?

DNAH2 p.Arg3426Gln (c.10277G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DNAH2 p.Arg3426Gln (c.10277G>A) in the general population?

DNAH2 p.Arg3426Gln (c.10277G>A) is ultra-rare (popmax 0.0378%, nfe) (gnomAD).

What do computational predictors say about DNAH2 p.Arg3426Gln (c.10277G>A)?

AlphaMissense predicts likely benign (score 0.0888) — an in-silico prediction, not a clinical call.

DNAH2 p.Arg3426Gln

c.10277G>A · rs201968584 · VCV2561514

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0888 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0378%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0888	likely benign
REVEL	0.076	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.4	GERP 0.58, phastCons 0.008
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 4.5e-10 · regional, not allelic
Overall
CADD	13.31	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0378% European (non-Finnish) · 446/1,180,030 alleles

Filtering AF 0.0348% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0337%

Overall 0.0321% 518/1,613,916 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0378%	2,646
Remaining individualsnot grpmax-eligible	0.0352%	2,840
Middle Eastern	0.0329%	3,042
Finnishnot grpmax-eligible	0.0266%	3,764
Admixed American	0.0217%	4,614
South Asian	0.0165%	6,072
African / African-American	0.00267%	37,428
East Asian	0.00223%	44,890

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.Arg3426Gln
Coding: c.10277G>A
MANE Select: NM_020877
dbSNP: rs201968584
Type: single nucleotide variant
Location: chr17:7817986 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI <0.01 (gnomAD)
Residue 3426: the 'aaa 5' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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DNAH2 p.Gln2069Glu Uncertain significance ★★ same condition
DNAH2 p.Ile4043Ser Uncertain significance ★★ ⚠ same condition
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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-arg3426gln (accessed [today's date]).

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