Is DHX16 p.Arg264Gln (c.791G>A) pathogenic?

DHX16 p.Arg264Gln (c.791G>A) is classified Uncertain significance in DHX16 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.069); Ultra-rare (popmax 0.0433%, amr); Associated with Inborn genetic diseases.

What condition is associated with DHX16 p.Arg264Gln (c.791G>A)?

DHX16 p.Arg264Gln (c.791G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DHX16 p.Arg264Gln (c.791G>A) in the general population?

DHX16 p.Arg264Gln (c.791G>A) is ultra-rare (popmax 0.0433%, amr) (gnomAD).

What do computational predictors say about DHX16 p.Arg264Gln (c.791G>A)?

AlphaMissense predicts likely benign (score 0.069) — an in-silico prediction, not a clinical call.

DHX16 p.Arg264Gln

c.791G>A · rs149882569 · VCV2372047

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.069 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0433%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.069	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -6.75	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 0.82	phastCons 0.31
Regional constraint	o/e 0.82	unconstrained · MANE · 7,978 bp · p 3.3e-05 · regional, not allelic
Overall
CADD	19.72	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 0.0433% Admixed American · 26/60,026 alleles

Filtering AF 0.0303% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.026%

Overall 0.00316% 51/1,612,956 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0433%	2,309
Remaining individualsnot grpmax-eligible	0.0032%	31,248
African / African-American	0.00267%	37,517
European (non-Finnish)	0.00169%	59,002
South Asian	0.0011%	91,088

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.Arg264Gln
Coding: c.791G>A
MANE Select: NM_003587
dbSNP: rs149882569
Type: single nucleotide variant
Location: chr6:30665609 (GRCh38)
Gene constraint: LOEUF 0.716 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.82 · 12 PDB
Residue 264: an α-helix

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

Similar variants

DHX16 p.Arg264Trp Uncertain significance ★ ⚠ same residue
DHX16 p.Arg940Cys Uncertain significance ★★ ⚠ same condition
DHX16 p.Arg956Gln Uncertain significance ★★ ⚠ same condition
DHX16 p.Glu105Lys Uncertain significance ★★ ⚠ same condition
DHX16 p.Glu995Gly Uncertain significance ★★ ⚠ same condition
DHX16 p.Ala215Val Uncertain significance ★ ⚠ same condition
DHX16 p.Ala34Ser Uncertain significance ★ ⚠ same condition
DHX16 p.Ala379Ser 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-arg264gln (accessed [today's date]).

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