Is DDX3X p.Ser57Arg (c.171T>G) pathogenic?

DDX3X p.Ser57Arg (c.171T>G) is classified Uncertain significance in DDX3X (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-25). AlphaMissense: likely pathogenic (0.7251); Absent from gnomAD v4.1.

How common is DDX3X p.Ser57Arg (c.171T>G) in the general population?

DDX3X p.Ser57Arg (c.171T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDX3X p.Ser57Arg (c.171T>G)?

AlphaMissense predicts likely pathogenic (score 0.7251) — an in-silico prediction, not a clinical call.

DDX3X p.Ser57Arg

c.171T>G · rs2519505296 · VCV2010629

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7251 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7251	likely pathogenic
REVEL	0.088	moderately benign-leaning
SaProt	LLR -8.03	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 8,391 bp · p 0.0057 · regional, not allelic
Overall
CADD	20.9	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.Ser57Arg
Coding: c.171T>G
MANE Select: NM_001356
dbSNP: rs2519505296
Type: single nucleotide variant
Location: chrX:41341503 (GRCh38)
Structure: AlphaFold pLDDT 73.24 · 17 PDB
Residue 57: the 'required for tbk1 and ikbke-dependent ifnb1 activation' region; the 'disordered' region

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

Similar variants

DDX3X p.Ser57Asn Benign/Likely benign ★★ ⚠ same residue
DDX3X p.Ser57Ile Uncertain significance ★ ⚠ same residue
DDX3X p.Ser57Thr Uncertain significance ★ ⚠ 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

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-ser57arg (accessed [today's date]).

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