Is DNAH2 p.Arg3242Trp (c.9724C>T) pathogenic?

DNAH2 p.Arg3242Trp (c.9724C>T) is classified Uncertain significance in DNAH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-07). AlphaMissense: likely benign (0.1903); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with DNAH2 p.Arg3242Trp (c.9724C>T)?

DNAH2 p.Arg3242Trp (c.9724C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DNAH2 p.Arg3242Trp (c.9724C>T) in the general population?

DNAH2 p.Arg3242Trp (c.9724C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DNAH2 p.Arg3242Trp (c.9724C>T)?

AlphaMissense predicts likely benign (score 0.1903) — an in-silico prediction, not a clinical call.

DNAH2 p.Arg3242Trp

c.9724C>T · VCV3841075

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1903 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1903	likely benign
REVEL	0.444	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 0.41, phastCons 0.99
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 4.5e-10 · regional, not allelic
Overall
CADD	26.0	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 0.00167% Admixed American · 1/60,002 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00106% 17/1,610,656 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,002
Finnishnot grpmax-eligible	0.00164%	60,920
European (non-Finnish)	0.00119%	84,270
South Asian	0.0011%	91,086

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.Arg3242Trp
Coding: c.9724C>T
MANE Select: NM_020877
Type: single nucleotide variant
Location: chr17:7807581 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI <0.01 (gnomAD)
Residue 3242: the 'stalk' 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

DNAH2 p.Ala1036Val Uncertain significance ★★ ⚠ same condition
DNAH2 p.Arg1533Cys Uncertain significance ★★ ⚠ same condition
DNAH2 p.Arg2538Gln Uncertain significance ★★ same condition
DNAH2 p.Arg3759His Uncertain significance ★★ ⚠ same condition
DNAH2 p.Gln2069Glu Uncertain significance ★★ same condition
DNAH2 p.Ile4043Ser Uncertain significance ★★ ⚠ same condition
DNAH2 p.Pro3819Leu Uncertain significance ★★ ⚠ same condition
DNAH2 p.Ala1058Thr Benign/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-arg3242trp (accessed [today's date]).

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