Is DHX38 p.Ala594= (c.1782C>G) pathogenic?

DHX38 p.Ala594= (c.1782C>G) is classified Likely benign in DHX38 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-21). Very rare (popmax 0.00667%, amr).

How common is DHX38 p.Ala594= (c.1782C>G) in the general population?

DHX38 p.Ala594= (c.1782C>G) is very rare (popmax 0.00667%, amr) (gnomAD).

DHX38 p.Ala594=

c.1782C>G · rs1417510711 · VCV1928282

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -0.59, phastCons 1
Overall
CADD	11.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/60,000 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000248% 4/1,613,668 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: DHX38
Protein: p.Ala594=
Coding: c.1782C>G
MANE Select: NM_014003
dbSNP: rs1417510711
Type: single nucleotide variant
Location: chr16:72103746 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.82 · 5 PDB
Residue 594: the helicase atp-binding domain; an α-helix

Full DHX38 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DHX38 c.2011-3C>A Uncertain significance ★★ same type
DHX38 c.2262+3G>C Uncertain significance ★★ same type
DHX38 c.2262+4C>T Uncertain significance ★★ same type
DHX38 c.2262+5G>A Uncertain significance ★★ same type
DHX38 c.2964+3G>C Uncertain significance ★★ same type
DHX38 c.616+3A>G Uncertain significance ★★ same type
DHX38 c.764+2T>G Uncertain significance ★★ same type
DHX38 p.Ala113Val Uncertain significance ★★ ⚠ same type

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/dhx38-p-ala594 (accessed [today's date]).

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