Is DHX16 p.Arg956Gln (c.2867G>A) pathogenic?

DHX16 p.Arg956Gln (c.2867G>A) is classified Uncertain significance in DHX16 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-09-17). AlphaMissense: likely benign (0.1865); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with DHX16 p.Arg956Gln (c.2867G>A)?

DHX16 p.Arg956Gln (c.2867G>A) is associated with Inborn genetic diseases, neuromuscular disease and ocular or auditory anomalies with or without seizures (ClinVar).

How common is DHX16 p.Arg956Gln (c.2867G>A) in the general population?

DHX16 p.Arg956Gln (c.2867G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about DHX16 p.Arg956Gln (c.2867G>A)?

AlphaMissense predicts likely benign (score 0.1865) — an in-silico prediction, not a clinical call.

DHX16 p.Arg956Gln

c.2867G>A · rs1447358889 · VCV2391229

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1865 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1865	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -9.53	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 2,969 bp · p 0.00052 · regional, not allelic
Overall
CADD	25.7	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 0.00133% African / African-American · 1/74,914 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000558% 9/1,612,884 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,914
European (non-Finnish)	0.000678%	147,503

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.Arg956Gln
Coding: c.2867G>A
MANE Select: NM_003587
dbSNP: rs1447358889
Type: single nucleotide variant
Location: chr6:30654836 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neuromuscular disease and ocular or auditory anomalies with or without seizures

Similar variants

DHX16 p.Thr674Met Pathogenic/Likely pathogenic ★★ same condition
DHX16 p.Arg940Cys Uncertain significance ★★ ⚠ same condition
DHX16 p.Asp580Gly Uncertain significance ★★ ⚠ same condition
DHX16 p.Glu105Lys Uncertain significance ★★ ⚠ same condition
DHX16 p.Glu995Gly 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-arg956gln (accessed [today's date]).

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