Is DHX38 p.Arg657= (c.1971C>T) pathogenic?

DHX38 p.Arg657= (c.1971C>T) is classified Benign in DHX38 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-27). Low-frequency (popmax 2.63%, afr).

How common is DHX38 p.Arg657= (c.1971C>T) in the general population?

DHX38 p.Arg657= (c.1971C>T) is low-frequency (popmax 2.63%, afr) (gnomAD).

DHX38 p.Arg657=

c.1971C>T · rs61757602 · VCV720840

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 2.63%, afr)

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 1.1	GERP 0.6, phastCons 1
Overall
CADD	11.79	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.63% African / African-American · 1,976/75,044 alleles

Filtering AF 2.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5%

Overall 0.137% 2,214/1,614,168 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.63%	38
Remaining individualsnot grpmax-eligible	0.163%	613
Admixed American	0.15%	667
Middle Eastern	0.099%	1,010
South Asian	0.00439%	22,770
European (non-Finnish)	0.00305%	32,779

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.Arg657=
Coding: c.1971C>T
MANE Select: NM_014003
dbSNP: rs61757602
Type: single nucleotide variant
Location: chr16:72104092 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.82 · 5 PDB
Residue 657: the helicase atp-binding domain

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

Similar variants

DHX38 p.Arg657His Likely benign ★ same residue
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

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-arg657 (accessed [today's date]).

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