Is DHX30 p.Pro82Leu (c.245C>T) pathogenic?

DHX30 p.Pro82Leu (c.245C>T) is classified Conflicting classifications of pathogenicity in DHX30 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2020-10-04). AlphaMissense: likely benign (0.1601); Very rare (popmax 0.00444%, sas); Associated with neurodevelopmental disorder with severe motor impairment and absent language.

What condition is associated with DHX30 p.Pro82Leu (c.245C>T)?

DHX30 p.Pro82Leu (c.245C>T) is associated with neurodevelopmental disorder with severe motor impairment and absent language (ClinVar).

How common is DHX30 p.Pro82Leu (c.245C>T) in the general population?

DHX30 p.Pro82Leu (c.245C>T) is very rare (popmax 0.00444%, sas) (gnomAD).

What do computational predictors say about DHX30 p.Pro82Leu (c.245C>T)?

AlphaMissense predicts likely benign (score 0.1601) — an in-silico prediction, not a clinical call.

DHX30 p.Pro82Leu

c.245C>T · rs769576678 · VCV1066052

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1601 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00444%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neurodevelopmental disorder with severe motor impairment and absent language

Computational evidence

Protein change
AlphaMissense	0.1601	likely benign
REVEL	0.221	benign-leaning
SaProt	LLR -7.08	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 2.2, phastCons 1
Regional constraint	o/e 0.43	unconstrained · MANE · 30 kb · p 1.4e-12 · regional, not allelic
Overall
CADD	24.6	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 0.00444% South Asian · 4/90,138 alleles

Filtering AF 0.00144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000898%

Overall 0.000343% 5/1,457,948 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00444%	22,535
European (non-Finnish)	8.48e-05%	1,178,606

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.Pro82Leu
Coding: c.245C>T
MANE Select: NM_138615
dbSNP: rs769576678
Type: single nucleotide variant
Location: chr3:47827467 (GRCh38)
Gene constraint: LOEUF 0.08 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.09 · 1 PDB
Residue 82: the drbm domain; a β-strand

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-pro82leu (accessed [today's date]).

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