Is DHX16 p.Arg640Trp (c.1918C>T) pathogenic?

DHX16 p.Arg640Trp (c.1918C>T) is classified Uncertain significance in DHX16 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: ambiguous (0.3777); Ultra-rare (popmax 0.0143%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DHX16 p.Arg640Trp (c.1918C>T)?

DHX16 p.Arg640Trp (c.1918C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DHX16 p.Arg640Trp (c.1918C>T) in the general population?

DHX16 p.Arg640Trp (c.1918C>T) is ultra-rare (popmax 0.0143%, nfe) (gnomAD).

What do computational predictors say about DHX16 p.Arg640Trp (c.1918C>T)?

AlphaMissense predicts ambiguous (score 0.3777) — an in-silico prediction, not a clinical call.

DHX16 p.Arg640Trp

c.1918C>T · rs143108219 · VCV2289596

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3777 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3777	ambiguous
REVEL	0.193	benign-leaning
SaProt	LLR -12.14	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 8,647 bp · p 7.4e-23 · regional, not allelic
Overall
CADD	29.7	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 0.0143% European (non-Finnish) · 169/1,179,886 alleles

Filtering AF 0.0125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0119%

Overall 0.0113% 182/1,612,842 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0143%	6,982
African / African-American	0.00668%	14,980
Remaining individualsnot grpmax-eligible	0.00641%	15,608
East Asian	0.00446%	22,441
Finnishnot grpmax-eligible	0.00158%	63,194
South Asian	0.0011%	91,008

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.Arg640Trp
Coding: c.1918C>T
MANE Select: NM_003587
dbSNP: rs143108219
Type: single nucleotide variant
Location: chr6:30659561 (GRCh38)
Gene constraint: LOEUF 0.716 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.82 · 12 PDB
Residue 640: the helicase c-terminal domain

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-arg640trp (accessed [today's date]).

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