Is DDX53 p.Phe96Ser (c.287T>C) pathogenic?

DDX53 p.Phe96Ser (c.287T>C) is classified Uncertain significance in DDX53 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-26). AlphaMissense: likely benign (0.2293); Ultra-rare (popmax 0.021%, afr).

How common is DDX53 p.Phe96Ser (c.287T>C) in the general population?

DDX53 p.Phe96Ser (c.287T>C) is ultra-rare (popmax 0.021%, afr) (gnomAD).

What do computational predictors say about DDX53 p.Phe96Ser (c.287T>C)?

AlphaMissense predicts likely benign (score 0.2293) — an in-silico prediction, not a clinical call.

DDX53 p.Phe96Ser

c.287T>C · rs147778026 · VCV3081119

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2293 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.021%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2293	likely benign
REVEL	0.136	moderately benign-leaning
SaProt	LLR -7.86	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 0.2	GERP -4, phastCons 0.025
Regional constraint	o/e 0.99	unconstrained · MANE · 1,892 bp · p 0.85 · regional, not allelic
Overall
CADD	17.64	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 0.021% African / African-American · 12/57,020 alleles

Filtering AF 0.0121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00952%

Overall 0.00124% 15/1,206,931 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.021%	4,752
Admixed American	0.00444%	22,529
Remaining individualsnot grpmax-eligible	0.00211%	47,421

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.Phe96Ser
Coding: c.287T>C
MANE Select: NM_182699
dbSNP: rs147778026
Type: single nucleotide variant
Location: chrX:23000344 (GRCh38)
Structure: AlphaFold pLDDT 79.66 · 2 PDB
Residue 96: 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-phe96ser (accessed [today's date]).

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