Is DDX50 p.Trp7Ser (c.20G>C) pathogenic?

DDX50 p.Trp7Ser (c.20G>C) is classified Uncertain significance in DDX50 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-10). AlphaMissense: likely benign (0.1489); Ultra-rare (popmax 0.0313%, nfe).

How common is DDX50 p.Trp7Ser (c.20G>C) in the general population?

DDX50 p.Trp7Ser (c.20G>C) is ultra-rare (popmax 0.0313%, nfe) (gnomAD).

What do computational predictors say about DDX50 p.Trp7Ser (c.20G>C)?

AlphaMissense predicts likely benign (score 0.1489) — an in-silico prediction, not a clinical call.

DDX50 p.Trp7Ser

c.20G>C · rs530795940 · VCV2399039

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1489 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0313%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1489	likely benign
REVEL	0.173	moderately benign-leaning
SaProt	LLR -2.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.5	GERP 2.1, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.71 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0313% European (non-Finnish) · 362/1,156,476 alleles

Filtering AF 0.0286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0275%

Overall 0.0242% 379/1,566,678 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0313%	3,195
Remaining individualsnot grpmax-eligible	0.0165%	6,069
Admixed American	0.00567%	17,647
African / African-American	0.00409%	24,466
Finnishnot grpmax-eligible	0.00164%	61,072

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: DDX50
Protein: p.Trp7Ser
Coding: c.20G>C
MANE Select: NM_024045
dbSNP: rs530795940
Type: single nucleotide variant
Location: chr10:68901404 (GRCh38)
Gene constraint: LOEUF 0.778 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.89 · 1 PDB
Residue 7: the 'disordered' region

Full DDX50 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDX50 p.Trp7Gly Uncertain significance ★ ⚠ same residue
DDX50 p.Ala659Thr Benign ★★ same type
DDX50 p.Ser239= Benign ★★ same type
DDX50 p.Ala138Asp Uncertain significance ★ ⚠ same type
DDX50 p.Ala138Gly Uncertain significance ★ ⚠ same type
DDX50 p.Ala241Val Uncertain significance ★ ⚠ same type
DDX50 p.Ala392Ser Uncertain significance ★ ⚠ same type
DDX50 p.Ala406Gly 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/ddx50-p-trp7ser (accessed [today's date]).

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