Is DDX59 p.Val91Phe (c.271G>T) pathogenic?

DDX59 p.Val91Phe (c.271G>T) is classified Uncertain significance in DDX59 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely pathogenic (0.5694); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DDX59 p.Val91Phe (c.271G>T)?

DDX59 p.Val91Phe (c.271G>T) is associated with Inborn genetic diseases (ClinVar).

How common is DDX59 p.Val91Phe (c.271G>T) in the general population?

DDX59 p.Val91Phe (c.271G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDX59 p.Val91Phe (c.271G>T)?

AlphaMissense predicts likely pathogenic (score 0.5694) — an in-silico prediction, not a clinical call.

DDX59 p.Val91Phe

c.271G>T · VCV4239028

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5694 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5694	likely pathogenic
REVEL	0.177	moderately benign-leaning
SaProt	LLR -11.56	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 1.1, phastCons 0.92
Regional constraint	o/e 0.92	unconstrained · MANE · 22 kb · p 0.03 · regional, not allelic
Overall
CADD	22.1	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: DDX59
Protein: p.Val91Phe
Coding: c.271G>T
MANE Select: NM_001031725
Type: single nucleotide variant
Location: chr1:200666470 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.71 · 1 PDB
Residue 91: the 'disordered' region

Full DDX59 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DDX59 p.Arg318His Uncertain significance ★★ ⚠ same condition
DDX59 p.Glu179Gly Uncertain significance ★★ ⚠ same condition
DDX59 p.Glu30Lys Uncertain significance ★★ ⚠ same condition
DDX59 p.His400Gln Uncertain significance ★★ ⚠ same condition
DDX59 p.Ile609Asn Uncertain significance ★★ ⚠ same condition
DDX59 p.Ile9Met Uncertain significance ★★ ⚠ same condition
DDX59 p.Ala50Pro Likely benign ★★ same condition
DDX59 p.Ser84Thr Likely benign ★★ same condition

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/ddx59-p-val91phe (accessed [today's date]).

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