Is DNAH2 p.Arg2689His (c.8066G>A) pathogenic?

DNAH2 p.Arg2689His (c.8066G>A) is classified Uncertain significance in DNAH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-27). AlphaMissense: likely benign (0.0813); Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with DNAH2 p.Arg2689His (c.8066G>A)?

DNAH2 p.Arg2689His (c.8066G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DNAH2 p.Arg2689His (c.8066G>A) in the general population?

DNAH2 p.Arg2689His (c.8066G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about DNAH2 p.Arg2689His (c.8066G>A)?

AlphaMissense predicts likely benign (score 0.0813) — an in-silico prediction, not a clinical call.

DNAH2 p.Arg2689His

c.8066G>A · rs1405281303 · VCV3083863

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0813 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0813	likely benign
REVEL	0.047	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 9.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 5,115 bp · p 3.1e-10 · regional, not allelic
Overall
CADD	23.7	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000496% 8/1,614,018 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.00267%	37,454
East Asian	0.00223%	44,902
Admixed American	0.00167%	59,994
European (non-Finnish)	0.000254%	393,345

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.Arg2689His
Coding: c.8066G>A
MANE Select: NM_020877
dbSNP: rs1405281303
Type: single nucleotide variant
Location: chr17:7797516 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI <0.01 (gnomAD)

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-arg2689his (accessed [today's date]).

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