Is DHX58 p.Ser477fs (c.1429_1430del) pathogenic?

DHX58 p.Ser477fs (c.14291430del) is classified Likely benign in DHX58 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Rare (popmax 0.306%, sas).

How common is DHX58 p.Ser477fs (c.1429_1430del) in the general population?

DHX58 p.Ser477fs (c.1429_1430del) is rare (popmax 0.306%, sas) (gnomAD).

DHX58 p.Ser477fs

c.1429_1430del · rs575525486 · VCV725550

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.306%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4.9	GERP -3.9
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.306% South Asian · 279/91,070 alleles

Filtering AF 0.277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.265%

Overall 0.0214% 345/1,613,858 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.306%	326
Remaining individualsnot grpmax-eligible	0.0176%	5,682
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.00449%	22,263
African / African-American	0.00133%	74,964

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.Ser477fs
Coding: c.1429_1430del
MANE Select: NM_024119
dbSNP: rs575525486
Type: Microsatellite
Location: chr17:42104899 (GRCh38)
Gene constraint: LOEUF 0.958 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.15 · 5 PDB
Residue 477: the helicase c-terminal domain

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

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-ser477fs (accessed [today's date]).

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