Is DHX30 p.Pro170Arg (c.509C>G) pathogenic?

DHX30 p.Pro170Arg (c.509C>G) is classified Conflicting classifications of pathogenicity in DHX30 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-03-29). AlphaMissense: likely benign (0.0803); Very rare (popmax 0.00517%, nfe); Associated with neurodevelopmental disorder with severe motor impairment and absent language.

What condition is associated with DHX30 p.Pro170Arg (c.509C>G)?

DHX30 p.Pro170Arg (c.509C>G) is associated with neurodevelopmental disorder with severe motor impairment and absent language (ClinVar).

How common is DHX30 p.Pro170Arg (c.509C>G) in the general population?

DHX30 p.Pro170Arg (c.509C>G) is very rare (popmax 0.00517%, nfe) (gnomAD).

What do computational predictors say about DHX30 p.Pro170Arg (c.509C>G)?

AlphaMissense predicts likely benign (score 0.0803) — an in-silico prediction, not a clinical call.

DHX30 p.Pro170Arg

c.509C>G · rs61757585 · VCV2440778

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0803 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00517%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neurodevelopmental disorder with severe motor impairment and absent language

Computational evidence

Protein change
AlphaMissense	0.0803	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -6.38	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 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 701 bp · p 0.37 · regional, not allelic
Overall
CADD	23.0	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

Grpmax group 0.00517% European (non-Finnish) · 61/1,180,034 alleles

Filtering AF 0.0041% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00372%

Overall 0.00397% 64/1,614,062 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00517%	19,345
African / African-American	0.00267%	37,459
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Pro170Arg
Coding: c.509C>G
MANE Select: NM_138615
dbSNP: rs61757585
Type: single nucleotide variant
Location: chr3:47841019 (GRCh38)
Gene constraint: LOEUF 0.08 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.09 · 1 PDB
Residue 170: the 'disordered' region

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-pro170arg (accessed [today's date]).

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