Is DHX30 p.Arg797Ter (c.2389C>T) pathogenic?

DHX30 p.Arg797Ter (c.2389C>T) is classified Pathogenic in DHX30 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-02-27). Very rare (popmax 8.47e-05%, nfe); Associated with neurodevelopmental disorder with severe motor impairment and absent language.

What condition is associated with DHX30 p.Arg797Ter (c.2389C>T)?

DHX30 p.Arg797Ter (c.2389C>T) is associated with neurodevelopmental disorder with severe motor impairment and absent language (ClinVar).

How common is DHX30 p.Arg797Ter (c.2389C>T) in the general population?

DHX30 p.Arg797Ter (c.2389C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

DHX30 p.Arg797Ter

c.2389C>T · rs1303348930 · VCV2443976

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

neurodevelopmental disorder with severe motor impairment and absent language

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 15 of 22
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.99	GERP 0.18, phastCons 0.31
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,968 alleles

Overall 6.84e-05% 1/1,461,498 alleles · very rare

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: DHX30
Protein: p.Arg797Ter
Coding: c.2389C>T
MANE Select: NM_138615
dbSNP: rs1303348930
Type: single nucleotide variant
Location: chr3:47848282 (GRCh38)
Gene constraint: LOEUF 0.08 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.09 · 1 PDB
Residue 797: the helicase c-terminal 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.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
DHX30 p.Cys1183Ser 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-arg797ter (accessed [today's date]).

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