Is DNAH2 p.Arg1626Trp (c.4876C>T) pathogenic?

DNAH2 p.Arg1626Trp (c.4876C>T) is classified Uncertain significance in DNAH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-18). AlphaMissense: likely benign (0.1637); Rare (popmax 0.214%, mid); Associated with Inborn genetic diseases.

What condition is associated with DNAH2 p.Arg1626Trp (c.4876C>T)?

DNAH2 p.Arg1626Trp (c.4876C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DNAH2 p.Arg1626Trp (c.4876C>T) in the general population?

DNAH2 p.Arg1626Trp (c.4876C>T) is rare (popmax 0.214%, mid) (gnomAD).

What do computational predictors say about DNAH2 p.Arg1626Trp (c.4876C>T)?

AlphaMissense predicts likely benign (score 0.1637) — an in-silico prediction, not a clinical call.

DNAH2 p.Arg1626Trp

c.4876C>T · rs145092294 · VCV2385162

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1637 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.214%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1637	likely benign
REVEL	0.449	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 73 kb · p 9.6e-12 · regional, not allelic
Overall
CADD	27.1	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 0.214% Middle Eastern · 13/6,062 alleles

Filtering AF 0.127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.101%

Overall 0.0156% 252/1,614,114 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.214%	466
South Asian	0.0406%	2,462
Remaining individualsnot grpmax-eligible	0.0272%	3,676
Admixed American	0.02%	5,002
European (non-Finnish)	0.0144%	6,941
African / African-American	0.004%	25,012

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.Arg1626Trp
Coding: c.4876C>T
MANE Select: NM_020877
dbSNP: rs145092294
Type: single nucleotide variant
Location: chr17:7776078 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI <0.01 (gnomAD)
Residue 1626: the 'stem' 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.Arg1626Gln Uncertain significance ★ ⚠ same residue
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

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-arg1626trp (accessed [today's date]).

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