Is DDX11 p.Pro182Arg (c.545C>G) pathogenic?

DDX11 p.Pro182Arg (c.545C>G) is classified Uncertain significance in DDX11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: likely benign (0.0784); Ultra-rare (popmax 0.0515%, amr).

How common is DDX11 p.Pro182Arg (c.545C>G) in the general population?

DDX11 p.Pro182Arg (c.545C>G) is ultra-rare (popmax 0.0515%, amr) (gnomAD).

What do computational predictors say about DDX11 p.Pro182Arg (c.545C>G)?

AlphaMissense predicts likely benign (score 0.0784) — an in-silico prediction, not a clinical call.

DDX11 p.Pro182Arg

c.545C>G · VCV4535695

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0784 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0515%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0784	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -6.35	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 -0.16	GERP -0.54
Regional constraint	o/e 0.79	unconstrained · MANE · 11 kb · p 5.3e-05 · regional, not allelic
Overall
CADD	1.346	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 0.0515% Admixed American · 30/58,268 alleles

Filtering AF 0.037% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0321%

Overall 0.00267% 43/1,609,562 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0515%	1,942
East Asian	0.00679%	14,733
South Asian	0.00111%	90,490
European (non-Finnish)	0.000763%	130,988

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.Pro182Arg
Coding: c.545C>G
MANE Select: NM_030653
Type: single nucleotide variant
Location: chr12:31085033 (GRCh38)
Gene constraint: LOEUF 0.781 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.77
Residue 182: the helicase atp-binding domain

Full DDX11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDX11 p.Pro182Leu Benign/Likely benign ★★ same residue
DDX11 p.Pro182= Likely benign ★ same residue
DDX11 c.1763-1G>C Pathogenic ★★ same type
DDX11 c.1949-1G>A Pathogenic/Likely pathogenic ★★ same type
DDX11 c.792+1G>A Likely pathogenic ★★ same type
DDX11 p.Arg140Ter Likely pathogenic ★★ same type
DDX11 p.Arg263Gln Pathogenic/Likely pathogenic ★★ same type
DDX11 p.Arg558Ter Pathogenic/Likely pathogenic ★★ same type

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-pro182arg (accessed [today's date]).

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