Is DDX53 p.Pro50Ser (c.148C>T) pathogenic?

DDX53 p.Pro50Ser (c.148C>T) is classified Uncertain significance in DDX53 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). AlphaMissense: likely benign (0.1694); Very rare (popmax 0.000113%, nfe).

How common is DDX53 p.Pro50Ser (c.148C>T) in the general population?

DDX53 p.Pro50Ser (c.148C>T) is very rare (popmax 0.000113%, nfe) (gnomAD).

What do computational predictors say about DDX53 p.Pro50Ser (c.148C>T)?

AlphaMissense predicts likely benign (score 0.1694) — an in-silico prediction, not a clinical call.

DDX53 p.Pro50Ser

c.148C>T · VCV3893324

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1694 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000113%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1694	likely benign
REVEL	0.16	moderately benign-leaning
SaProt	LLR -11.41	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP 0.99, phastCons 0.003
Regional constraint	o/e 0.99	unconstrained · MANE · 1,892 bp · p 0.85 · regional, not allelic
Overall
CADD	19.08	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

Grpmax group 0.000113% European (non-Finnish) · 1/886,772 alleles

Overall 9.24e-05% 1/1,081,957 alleles · very rare

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: DDX53
Protein: p.Pro50Ser
Coding: c.148C>T
MANE Select: NM_182699
Type: single nucleotide variant
Location: chrX:23000205 (GRCh38)
Structure: AlphaFold pLDDT 79.66 · 2 PDB
Residue 50: the kh domain

Full DDX53 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDX53 p.Ala107Ser Benign ★★ same type
DDX53 p.Gly499Val Benign ★★ ⚠ same type
DDX53 p.Ile134Val Likely benign ★★ same type
DDX53 p.Ser326Asn Likely pathogenic ★ ⚠ same type
DDX53 p.Ala11Gly Uncertain significance ★ ⚠ same type
DDX53 p.Ala437Val Uncertain significance ★ ⚠ same type
DDX53 p.Ala480Ser Uncertain significance ★ ⚠ same type
DDX53 p.Ala579Val Uncertain significance ★ ⚠ 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/ddx53-p-pro50ser (accessed [today's date]).

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