Is DDX11 p.Arg348= (c.1042C>A) pathogenic?

DDX11 p.Arg348= (c.1042C>A) is classified Likely benign in DDX11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). Ultra-rare (popmax 0.0173%, sas).

How common is DDX11 p.Arg348= (c.1042C>A) in the general population?

DDX11 p.Arg348= (c.1042C>A) is ultra-rare (popmax 0.0173%, sas) (gnomAD).

DDX11 p.Arg348=

c.1042C>A · VCV4535711

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.31	GERP -3.4
Overall
CADD	9.824	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0173% South Asian · 14/80,780 alleles

Filtering AF 0.0132% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0125%

Overall 0.0146% 216/1,480,784 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0174%	5,752
South Asiangrpmax	0.0173%	5,770
Finnishnot grpmax-eligible	0.0169%	5,932
European (non-Finnish)	0.0151%	6,636
Admixed American	0.014%	7,146
African / African-American	0.0127%	7,898
Ashkenazi Jewishnot grpmax-eligible	0.00359%	27,880
East Asian	0.00245%	40,798

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg348=
Coding: c.1042C>A
MANE Select: NM_030653
Type: single nucleotide variant
Location: chr12:31090047 (GRCh38)
Gene constraint: LOEUF 0.781 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.77
Residue 348: the helicase atp-binding domain

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

Similar variants

DDX11 p.Arg348Trp Uncertain significance ★ ⚠ 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
DDX11 p.Arg75Ter 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-arg348 (accessed [today's date]).

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