Is DNAH3 p.Arg1021Trp (c.3061C>T) pathogenic?

DNAH3 p.Arg1021Trp (c.3061C>T) is classified Uncertain significance in DNAH3 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-06-17). AlphaMissense: likely benign (0.2016); Ultra-rare (popmax 0.0284%, amr).

How common is DNAH3 p.Arg1021Trp (c.3061C>T) in the general population?

DNAH3 p.Arg1021Trp (c.3061C>T) is ultra-rare (popmax 0.0284%, amr) (gnomAD).

What do computational predictors say about DNAH3 p.Arg1021Trp (c.3061C>T)?

AlphaMissense predicts likely benign (score 0.2016) — an in-silico prediction, not a clinical call.

DNAH3 p.Arg1021Trp

c.3061C>T · VCV3272813

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2016 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0284%, amr)

Computational evidence

Protein change
AlphaMissense	0.2016	likely benign
REVEL	0.391	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -1.1, phastCons 1
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R1067W vs ClinVar R1021W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0284% Admixed American · 17/59,960 alleles

Filtering AF 0.018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00288% 46/1,599,760 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0284%	3,527
Remaining individualsnot grpmax-eligible	0.00968%	10,335
African / African-American	0.00268%	37,321
European (non-Finnish)	0.0018%	55,581

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: DNAH3
Protein: p.Arg1021Trp
Coding: c.3061C>T
MANE Select: NM_001347886
Type: single nucleotide variant
Location: chr16:21070712 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI <0.01 (gnomAD)
Residue 1021: the 'stem' region

Full DNAH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAH3 p.Arg1021Gln Uncertain significance ★ ⚠ same residue
DNAH3 p.Ala1918Gly Uncertain significance ★★ ⚠ same type
DNAH3 p.Arg1228Gln Uncertain significance ★★ same type
DNAH3 p.Arg635Gln Uncertain significance ★★ same type
DNAH3 p.Asn1728Ser Uncertain significance ★★ ⚠ same type
DNAH3 p.Asp3656Asn Uncertain significance ★★ same type
DNAH3 p.Leu2597Val Uncertain significance ★★ same type
DNAH3 p.Leu4044Phe Uncertain significance ★★ ⚠ same type

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/dnah3-p-arg1021trp (accessed [today's date]).

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