Is DHX58 p.Arg69Cys (c.205C>T) pathogenic?

DHX58 p.Arg69Cys (c.205C>T) is classified Uncertain significance in DHX58 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-27). AlphaMissense: likely benign (0.1001); Very rare (popmax 0.00668%, eas).

How common is DHX58 p.Arg69Cys (c.205C>T) in the general population?

DHX58 p.Arg69Cys (c.205C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about DHX58 p.Arg69Cys (c.205C>T)?

AlphaMissense predicts likely benign (score 0.1001) — an in-silico prediction, not a clinical call.

DHX58 p.Arg69Cys

c.205C>T · rs782702291 · VCV3082331

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1001 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1001	likely benign
REVEL	0.12	moderately benign-leaning
SaProt	LLR -10.49	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.084	GERP -2.3
Regional constraint	o/e 0.87	unconstrained · MANE · 10 kb · p 7e-05 · regional, not allelic
Overall
CADD	21.4	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 0.00668% East Asian · 3/44,898 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000991% 16/1,613,974 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,966
African / African-American	0.00133%	74,928
South Asian	0.0011%	91,090
European (non-Finnish)	0.000932%	107,275

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: DHX58
Protein: p.Arg69Cys
Coding: c.205C>T
MANE Select: NM_024119
dbSNP: rs782702291
Type: single nucleotide variant
Location: chr17:42111461 (GRCh38)
Gene constraint: LOEUF 0.958 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.15 · 5 PDB
Residue 69: the helicase atp-binding domain

Full DHX58 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DHX58 p.Arg69Ser Uncertain significance ★ ⚠ same residue
DHX58 p.Gln425Arg Benign ★★ same type
DHX58 p.Ala110Thr Uncertain significance ★ ⚠ same type
DHX58 p.Ala302Pro Uncertain significance ★ ⚠ same type
DHX58 p.Ala304Val Uncertain significance ★ ⚠ same type
DHX58 p.Ala342Val Uncertain significance ★ ⚠ same type
DHX58 p.Ala35Val Uncertain significance ★ ⚠ same type
DHX58 p.Ala480Gly 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/dhx58-p-arg69cys (accessed [today's date]).

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