Is DDX3X p.Pro274Ala (c.820C>G) pathogenic?

DDX3X p.Pro274Ala (c.820C>G) is classified Pathogenic in DDX3X (ClinVar, Single submitter, 2 submitters; last evaluated 2023-08-07). AlphaMissense: likely pathogenic (0.9975); Absent from gnomAD v4.1.

How common is DDX3X p.Pro274Ala (c.820C>G) in the general population?

DDX3X p.Pro274Ala (c.820C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDX3X p.Pro274Ala (c.820C>G)?

AlphaMissense predicts likely pathogenic (score 0.9975) — an in-silico prediction, not a clinical call.

DDX3X p.Pro274Ala

c.820C>G · VCV3361840

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9975 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9975	likely pathogenic ✓ concordant with ClinVar
REVEL	0.629	indeterminate
SaProt	LLR -13.87	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.24	constrained · MANE · 3,927 bp · p 1.5e-39 · regional, not allelic
Overall
CADD	27.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DDX3X
Protein: p.Pro274Ala
Coding: c.820C>G
MANE Select: NM_001356
Type: single nucleotide variant
Location: chrX:41344084 (GRCh38)
Structure: AlphaFold pLDDT 73.24 · 17 PDB
Residue 274: 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 p.Pro274Ser Likely pathogenic ★ same residue
DDX3X p.Pro274fs Pathogenic ★ same residue
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

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-pro274ala (accessed [today's date]).

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