Is DDX46 p.Ser754Arg (c.2260A>C) pathogenic?

DDX46 p.Ser754Arg (c.2260A>C) is classified Uncertain significance in DDX46 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-12). AlphaMissense: likely benign (0.2862); Absent from gnomAD v4.1.

How common is DDX46 p.Ser754Arg (c.2260A>C) in the general population?

DDX46 p.Ser754Arg (c.2260A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDX46 p.Ser754Arg (c.2260A>C)?

AlphaMissense predicts likely benign (score 0.2862) — an in-silico prediction, not a clinical call.

DDX46 p.Ser754Arg

c.2260A>C · rs2532119325 · VCV3081047

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2862 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2862	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -7.01	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 5.4	GERP 0.36, phastCons 1
Regional constraint	o/e 0.41	unconstrained · MANE · 29 kb · p 3.1e-40 · regional, not allelic
Overall
CADD	19.72	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

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: DDX46
Protein: p.Ser754Arg
Coding: c.2260A>C
MANE Select: NM_001300860
dbSNP: rs2532119325
Type: single nucleotide variant
Location: chr5:134811332 (GRCh38)
Gene constraint: LOEUF 0.292 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.22 · 6 PDB

Full DDX46 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDX46 p.Asn940Ser Uncertain significance ★★ ⚠ same type
DDX46 p.Ala178Thr Uncertain significance ★ ⚠ same type
DDX46 p.Arg101Gln Uncertain significance ★ ⚠ same type
DDX46 p.Arg410Gln Uncertain significance ★ ⚠ same type
DDX46 p.Arg545His Uncertain significance ★ ⚠ same type
DDX46 p.Asn116Thr Uncertain significance ★ ⚠ same type
DDX46 p.Asn698Ser Uncertain significance ★ ⚠ same type
DDX46 p.Asp77Glu 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/ddx46-p-ser754arg (accessed [today's date]).

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