Is DHX58 p.Ala302Pro (c.904G>C) pathogenic?

DHX58 p.Ala302Pro (c.904G>C) is classified Uncertain significance in DHX58 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: likely pathogenic (0.9093); Absent from gnomAD v4.1.

How common is DHX58 p.Ala302Pro (c.904G>C) in the general population?

DHX58 p.Ala302Pro (c.904G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DHX58 p.Ala302Pro (c.904G>C)?

AlphaMissense predicts likely pathogenic (score 0.9093) — an in-silico prediction, not a clinical call.

DHX58 p.Ala302Pro

c.904G>C · VCV4240403

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9093 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9093	likely pathogenic · top 5% in DHX58
REVEL	0.514	indeterminate
SaProt	LLR -14.85	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 10 kb · p 7e-05 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: DHX58
Protein: p.Ala302Pro
Coding: c.904G>C
MANE Select: NM_024119
Type: single nucleotide variant
Location: chr17:42107697 (GRCh38)
Gene constraint: LOEUF 0.958 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.15 · 5 PDB

Full DHX58 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DHX58 p.Gln425Arg Benign ★★ same type
DHX58 p.Ala110Thr Uncertain significance ★ ⚠ same type
DHX58 p.Ala304Val Uncertain significance ★ ⚠ same type
DHX58 p.Ala342Val Uncertain significance ★ ⚠ same type
DHX58 p.Ala35Val Uncertain significance ★ ⚠ same type
DHX58 p.Ala480Gly Uncertain significance ★ ⚠ same type
DHX58 p.Ala480Thr Uncertain significance ★ ⚠ same type
DHX58 p.Ala483Val 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/dhx58-p-ala302pro (accessed [today's date]).

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