Is DHX30 p.Pro583Leu (c.1748C>T) pathogenic?

DHX30 p.Pro583Leu (c.1748C>T) is classified Uncertain significance in DHX30 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-21). AlphaMissense: likely benign (0.2549); Ultra-rare (popmax 0.028%, afr); Associated with Inborn genetic diseases.

What condition is associated with DHX30 p.Pro583Leu (c.1748C>T)?

DHX30 p.Pro583Leu (c.1748C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DHX30 p.Pro583Leu (c.1748C>T) in the general population?

DHX30 p.Pro583Leu (c.1748C>T) is ultra-rare (popmax 0.028%, afr) (gnomAD).

What do computational predictors say about DHX30 p.Pro583Leu (c.1748C>T)?

AlphaMissense predicts likely benign (score 0.2549) — an in-silico prediction, not a clinical call.

DHX30 p.Pro583Leu

c.1748C>T · rs533941338 · VCV2407364

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2549 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.028%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2549	likely benign
REVEL	0.298	indeterminate
SaProt	LLR -11.29	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 38 bp · p 0.45 · regional, not allelic
Overall
CADD	29.3	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 0.028% African / African-American · 21/75,048 alleles

Filtering AF 0.0187% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0157%

Overall 0.00353% 57/1,612,858 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.028%	3,574
Admixed American	0.00501%	19,963
European (non-Finnish)	0.0028%	35,750

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.Pro583Leu
Coding: c.1748C>T
MANE Select: NM_138615
dbSNP: rs533941338
Type: single nucleotide variant
Location: chr3:47846820 (GRCh38)
Gene constraint: LOEUF 0.08 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.09 · 1 PDB
Residue 583: the helicase atp-binding domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DHX30 p.Arg1180Gln Uncertain significance ★★ ⚠ same condition
DHX30 p.Arg412Cys Uncertain significance ★★ ⚠ same condition
DHX30 p.Arg598Cys Uncertain significance ★★ ⚠ same condition
DHX30 p.Asn445Ser Uncertain significance ★★ ⚠ same condition
DHX30 p.Cys1183Ser Uncertain significance ★★ ⚠ same condition
DHX30 p.Glu228Gly Uncertain significance ★★ ⚠ same condition
DHX30 p.Leu650Phe Uncertain significance ★★ ⚠ same condition
DHX30 p.Pro392Leu 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-pro583leu (accessed [today's date]).

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