Is DDX3X p.Pro247= (c.741A>T) pathogenic?

DDX3X p.Pro247= (c.741A>T) is classified Likely benign in DDX3X (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-10). Very rare (popmax 0.000112%, nfe).

How common is DDX3X p.Pro247= (c.741A>T) in the general population?

DDX3X p.Pro247= (c.741A>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

DDX3X p.Pro247=

c.741A>T · rs2063885189 · VCV2877519

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

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 0.01	GERP -2.3, phastCons 0.035
Overall
CADD	6.535	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/894,130 alleles

Overall 0.000183% 2/1,095,889 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0021%	47,592
European (non-Finnish)grpmax	0.000112%	894,126

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: DDX3X
Protein: p.Pro247=
Coding: c.741A>T
MANE Select: NM_001356
dbSNP: rs2063885189
Type: single nucleotide variant
Location: chrX:41343798 (GRCh38)
Structure: AlphaFold pLDDT 73.24 · 17 PDB
Residue 247: an α-helix; the helicase atp-binding domain; the 'interaction with gsk3b' region

Full DDX3X gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDX3X c.1497+1G>A Likely pathogenic ★★ same type
DDX3X c.1498-2A>G Pathogenic ★★ same type
DDX3X c.151+1G>A Pathogenic ★★ same type
DDX3X c.1769+1G>A Pathogenic ★★ same type
DDX3X c.765+1G>A Pathogenic ★★ same type
DDX3X c.865-1G>A Pathogenic ★★ same type
DDX3X c.865-1G>C Pathogenic ★★ same type
DDX3X c.865-2A>G 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/ddx3x-p-pro247 (accessed [today's date]).

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