Is DHX16 p.Arg856Ter (c.2566C>T) pathogenic?

DHX16 p.Arg856Ter (c.2566C>T) is classified Uncertain significance in DHX16 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-30). Very rare (popmax 0.00329%, sas); Associated with neuromuscular disease and ocular or auditory anomalies with or without seizures.

What condition is associated with DHX16 p.Arg856Ter (c.2566C>T)?

DHX16 p.Arg856Ter (c.2566C>T) is associated with neuromuscular disease and ocular or auditory anomalies with or without seizures (ClinVar).

How common is DHX16 p.Arg856Ter (c.2566C>T) in the general population?

DHX16 p.Arg856Ter (c.2566C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

DHX16 p.Arg856Ter

c.2566C>T · rs891765304 · VCV1696591

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

neuromuscular disease and ocular or auditory anomalies with or without seizures

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 17 of 20
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,094 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00198% 32/1,612,950 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,365
European (non-Finnish)	0.0022%	45,386
Admixed American	0.00167%	60,000
Remaining individualsnot grpmax-eligible	0.0016%	62,478
African / African-American	0.00133%	74,918

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.Arg856Ter
Coding: c.2566C>T
MANE Select: NM_003587
dbSNP: rs891765304
Type: single nucleotide variant
Location: chr6:30655530 (GRCh38)
Gene constraint: LOEUF 0.716 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.82 · 12 PDB

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.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
DHX16 c.1126-3T>C 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/dhx16-p-arg856ter (accessed [today's date]).

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