Is DHX16 p.Arg736Cys (c.2206C>T) pathogenic?

DHX16 p.Arg736Cys (c.2206C>T) is classified Uncertain significance in DHX16 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-08). AlphaMissense: likely pathogenic (0.882); Very rare (popmax 0.00223%, eas); Associated with neuromuscular disease and ocular or auditory anomalies with or without seizures.

What condition is associated with DHX16 p.Arg736Cys (c.2206C>T)?

DHX16 p.Arg736Cys (c.2206C>T) is associated with neuromuscular disease and ocular or auditory anomalies with or without seizures (ClinVar).

How common is DHX16 p.Arg736Cys (c.2206C>T) in the general population?

DHX16 p.Arg736Cys (c.2206C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DHX16 p.Arg736Cys (c.2206C>T)?

AlphaMissense predicts likely pathogenic (score 0.882) — an in-silico prediction, not a clinical call.

DHX16 p.Arg736Cys

c.2206C>T · VCV4078477

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.882 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

neuromuscular disease and ocular or auditory anomalies with or without seizures

Computational evidence

Protein change
AlphaMissense	0.882	likely pathogenic
REVEL	0.465	indeterminate
SaProt	LLR -13.98	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 8,647 bp · p 7.4e-23 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00223% East Asian · 1/44,900 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000434% 7/1,613,408 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,900
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.000424%	236,009

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: DHX16
Protein: p.Arg736Cys
Coding: c.2206C>T
MANE Select: NM_003587
Type: single nucleotide variant
Location: chr6:30656702 (GRCh38)
Gene constraint: LOEUF 0.716 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.82 · 12 PDB
Residue 736: the helicase c-terminal domain; a β-strand

Full DHX16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neuromuscular disease and ocular or auditory anomalies with or without seizures — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DHX16 p.Arg736Ser Uncertain significance ★ ⚠ same residue
DHX16 p.Thr674Met Pathogenic/Likely pathogenic ★★ same condition
DHX16 p.Arg940Cys Uncertain significance ★★ ⚠ same condition
DHX16 p.Arg956Gln Uncertain significance ★★ ⚠ same condition
DHX16 p.Asp580Gly Uncertain significance ★★ ⚠ same condition
DHX16 p.Glu105Lys Uncertain significance ★★ ⚠ same condition
DHX16 p.Glu678Gly Likely pathogenic ★ same condition
DHX16 p.Ser17Ter Likely pathogenic ★ 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/dhx16-p-arg736cys (accessed [today's date]).

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