Is DHX34 p.Pro518= (c.1554A>G) pathogenic?

DHX34 p.Pro518= (c.1554A>G) is classified Benign in DHX34 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-06). Common (popmax 22.7%, afr) — too common for a highly-penetrant pathogenic allele; Associated with DHX34-related disorder.

What condition is associated with DHX34 p.Pro518= (c.1554A>G)?

DHX34 p.Pro518= (c.1554A>G) is associated with DHX34-related disorder (ClinVar).

DHX34 p.Pro518=

Q: How common is DHX34 p.Pro518= (c.1554A>G) in the general population?

DHX34 p.Pro518= (c.1554A>G) is common (popmax 22.7%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1554A>G · rs2547390 · VCV3059415

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 22.7%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

DHX34-related disorder

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 -20	GERP -3.8
Overall
CADD	0.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 22.7% African / African-American · 16,985/74,946 alleles

Filtering AF 22.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 22.3%

Overall 6.61% 106,693/1,612,972 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	22.7%	4
Admixed American	12.7%	8
East Asian	9.14%	11
Finnishnot grpmax-eligible	7.92%	13
Remaining individualsnot grpmax-eligible	7.25%	14
Middle Eastern	6.2%	16
European (non-Finnish)	5.3%	19
South Asian	4.58%	22
Ashkenazi Jewishnot grpmax-eligible	4.57%	22
Amishnot grpmax-eligible	0.987%	101

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: DHX34
Protein: p.Pro518=
Coding: c.1554A>G
MANE Select: NM_014681
dbSNP: rs2547390
Type: single nucleotide variant
Location: chr19:47362654 (GRCh38)
Gene constraint: LOEUF 1.047 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.85
Residue 518: a UniProt-annotated variant site (found in a patient with a neurodevelopmental disorder; uncertain significance); the helicase c-terminal domain

Full DHX34 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DHX34-related disorder

Similar variants

DHX34 p.Asn682Thr Uncertain significance ★★ ⚠ same condition
DHX34 p.Ser624Arg Uncertain significance ★★ ⚠ same condition
DHX34 p.Thr973Met Uncertain significance ★★ ⚠ same condition
DHX34 p.Ala347Val Uncertain significance ★ ⚠ same condition
DHX34 p.Asn441Ser Likely pathogenic ⚠ same condition
DHX34 p.Gln156Ter Likely pathogenic same condition
DHX34 c.1593+9T>C Benign same condition
DHX34 c.2707-10T>C Benign 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/dhx34-p-pro518 (accessed [today's date]).

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