Is DDX11 p.Arg900Trp (c.2698C>T) pathogenic?

DDX11 p.Arg900Trp (c.2698C>T) is classified Uncertain significance in DDX11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: likely benign (0.1005); Ultra-rare (popmax 0.0214%, afr); Associated with Inborn genetic diseases.

What condition is associated with DDX11 p.Arg900Trp (c.2698C>T)?

DDX11 p.Arg900Trp (c.2698C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DDX11 p.Arg900Trp (c.2698C>T) in the general population?

DDX11 p.Arg900Trp (c.2698C>T) is ultra-rare (popmax 0.0214%, afr) (gnomAD).

What do computational predictors say about DDX11 p.Arg900Trp (c.2698C>T)?

AlphaMissense predicts likely benign (score 0.1005) — an in-silico prediction, not a clinical call.

DDX11 p.Arg900Trp

c.2698C>T · rs140858176 · VCV3080886

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1005 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0214%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1005	likely benign
REVEL	0.358	indeterminate
SaProt	LLR -6.50	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.75 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.6	GERP -0.4, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 3,146 bp · p 0.001 · regional, not allelic
Overall
CADD	21.1	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P898L vs ClinVar R900W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0214% African / African-American · 16/74,888 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.00366% 59/1,613,720 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0214%	4,681
South Asian	0.00549%	18,212
Admixed American	0.005%	19,997
European (non-Finnish)	0.0028%	35,753
East Asian	0.00223%	44,888
Remaining individualsnot grpmax-eligible	0.0016%	62,460

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: DDX11
Protein: p.Arg900Trp
Coding: c.2698C>T
MANE Select: NM_030653
dbSNP: rs140858176
Type: single nucleotide variant
Location: chr12:31103813 (GRCh38)
Gene constraint: LOEUF 0.781 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.77

Full DDX11 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

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DDX11 c.2692-1G>A Uncertain significance ★★ same condition
DDX11 p.Ala380Ser Uncertain significance ★★ ⚠ same condition
DDX11 p.Ala742Val Uncertain significance ★★ ⚠ same condition
DDX11 p.Arg256Gln Uncertain significance ★★ ⚠ same condition
DDX11 p.Arg643His Uncertain significance ★★ ⚠ same condition
DDX11 p.Asn577Ser Uncertain significance ★★ ⚠ same condition
DDX11 p.Gln309His 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/ddx11-p-arg900trp (accessed [today's date]).

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