Is DNAH3 p.Asp696Asn (c.2086G>A) pathogenic?

DNAH3 p.Asp696Asn (c.2086G>A) is classified Uncertain significance in DNAH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-30). AlphaMissense: likely benign (0.1434); Ultra-rare (popmax 0.0245%, sas).

How common is DNAH3 p.Asp696Asn (c.2086G>A) in the general population?

DNAH3 p.Asp696Asn (c.2086G>A) is ultra-rare (popmax 0.0245%, sas) (gnomAD).

What do computational predictors say about DNAH3 p.Asp696Asn (c.2086G>A)?

AlphaMissense predicts likely benign (score 0.1434) — an in-silico prediction, not a clinical call.

DNAH3 p.Asp696Asn

c.2086G>A · VCV4242525

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1434 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1434	likely benign
REVEL	0.044	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 4.7	GERP 1.7, phastCons 1
Overall
CADD	20.8	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D756N vs ClinVar D696N) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0245% South Asian · 22/89,786 alleles

Filtering AF 0.0165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0139%

Overall 0.00179% 26/1,454,430 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0245%	4,081
Remaining individualsnot grpmax-eligible	0.00322%	31,062
East Asian	0.00223%	44,824
European (non-Finnish)	8.51e-05%	1,174,893

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.Asp696Asn
Coding: c.2086G>A
MANE Select: NM_001347886
Type: single nucleotide variant
Location: chr16:21106508 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI <0.01 (gnomAD)
Residue 696: the 'stem' region

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

Similar variants

DNAH3 p.Ala1918Gly Uncertain significance ★★ ⚠ same type
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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
DNAH3 p.Lys374Gln 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-asp696asn (accessed [today's date]).

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