Is DHX30 p.Arg466Pro (c.1397G>C) pathogenic?

DHX30 p.Arg466Pro (c.1397G>C) is classified Uncertain significance in DHX30 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-17). AlphaMissense: likely pathogenic (0.9975); Absent from gnomAD v4.1; Associated with neurodevelopmental disorder with severe motor impairment and absent language.

What condition is associated with DHX30 p.Arg466Pro (c.1397G>C)?

DHX30 p.Arg466Pro (c.1397G>C) is associated with neurodevelopmental disorder with severe motor impairment and absent language (ClinVar).

How common is DHX30 p.Arg466Pro (c.1397G>C) in the general population?

DHX30 p.Arg466Pro (c.1397G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DHX30 p.Arg466Pro (c.1397G>C)?

AlphaMissense predicts likely pathogenic (score 0.9975) — an in-silico prediction, not a clinical call.

DHX30 p.Arg466Pro

c.1397G>C · rs2549292832 · VCV3254749

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9975 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

neurodevelopmental disorder with severe motor impairment and absent language

Computational evidence

Protein change
AlphaMissense	0.9975	likely pathogenic · top 4% in DHX30
REVEL	0.335	indeterminate
SaProt	LLR -14.55	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 12	GERP -2.3, phastCons 1
Regional constraint	o/e 0.35	constrained · MANE · 377 bp · p 2.1e-18 · regional, not allelic
Overall
CADD	27.5	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: DHX30
Protein: p.Arg466Pro
Coding: c.1397G>C
MANE Select: NM_138615
dbSNP: rs2549292832
Type: single nucleotide variant
Location: chr3:47846469 (GRCh38)
Gene constraint: LOEUF 0.08 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.09 · 1 PDB
Residue 466: the helicase atp-binding domain

Full DHX30 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder with severe motor impairment and absent language — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DHX30 p.Arg466Leu Uncertain significance ★ ⚠ same residue
DHX30 p.Arg782Gln Pathogenic/Likely pathogenic ★★ same condition
DHX30 p.Arg782Trp Pathogenic ★★ same condition
DHX30 p.Arg785Cys Pathogenic/Likely pathogenic ★★ same condition
DHX30 p.Arg785His Pathogenic/Likely pathogenic ★★ same condition
DHX30 p.Arg412Cys Uncertain significance ★★ ⚠ same condition
DHX30 p.Arg779Cys Uncertain significance ★★ ⚠ same condition
DHX30 p.Asp712Asn Uncertain significance ★★ ⚠ 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/dhx30-p-arg466pro (accessed [today's date]).

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