Is DHX16 p.Arg281Trp (c.841C>T) pathogenic?

DHX16 p.Arg281Trp (c.841C>T) is classified Uncertain significance in DHX16 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely benign (0.1803); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with DHX16 p.Arg281Trp (c.841C>T)?

DHX16 p.Arg281Trp (c.841C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DHX16 p.Arg281Trp (c.841C>T) in the general population?

DHX16 p.Arg281Trp (c.841C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about DHX16 p.Arg281Trp (c.841C>T)?

AlphaMissense predicts likely benign (score 0.1803) — an in-silico prediction, not a clinical call.

DHX16 p.Arg281Trp

c.841C>T · rs771684063 · VCV2542501

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1803 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1803	likely benign
REVEL	0.114	moderately benign-leaning
SaProt	LLR -11.32	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 7,978 bp · p 3.3e-05 · regional, not allelic
Overall
CADD	26.4	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 0.00333% Admixed American · 2/60,000 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000372% 6/1,612,912 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,000
Remaining individualsnot grpmax-eligible	0.0016%	62,476
African / African-American	0.00133%	74,916
South Asian	0.0011%	91,086
European (non-Finnish)	8.47e-05%	1,180,036

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.Arg281Trp
Coding: c.841C>T
MANE Select: NM_003587
dbSNP: rs771684063
Type: single nucleotide variant
Location: chr6:30665559 (GRCh38)
Gene constraint: LOEUF 0.716 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.82 · 12 PDB
Residue 281: 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.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
DHX16 p.Ala512Gly 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-arg281trp (accessed [today's date]).

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