Is DHX38 p.Arg1056= (c.3168G>T) pathogenic?

DHX38 p.Arg1056= (c.3168G>T) is classified Likely benign in DHX38 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-01). Very rare (popmax 0.000763%, nfe).

How common is DHX38 p.Arg1056= (c.3168G>T) in the general population?

DHX38 p.Arg1056= (c.3168G>T) is very rare (popmax 0.000763%, nfe) (gnomAD).

DHX38 p.Arg1056=

c.3168G>T · rs768412606 · VCV2178649

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

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 2.7	GERP -1.1, phastCons 1
Overall
CADD	9.649	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000763% European (non-Finnish) · 9/1,180,034 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000752% 11/1,461,888 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,255
European (non-Finnish)grpmax	0.000763%	131,115

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg1056=
Coding: c.3168G>T
MANE Select: NM_014003
dbSNP: rs768412606
Type: single nucleotide variant
Location: chr16:72108520 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.82 · 5 PDB

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-arg1056 (accessed [today's date]).

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