Is DHX32 p.Val352fs (c.1053dup) pathogenic?

DHX32 p.Val352fs (c.1053dup) is classified Uncertain significance in DHX32 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-23). Very rare (popmax 8.47e-05%, nfe).

How common is DHX32 p.Val352fs (c.1053dup) in the general population?

DHX32 p.Val352fs (c.1053dup) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

DHX32 p.Val352fs

c.1053dup · rs2494422492 · VCV1966042

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 4 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.6	GERP -0.16, phastCons 0.9

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,962 alleles

Overall 0.000137% 2/1,461,690 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,496
European (non-Finnish)grpmax	8.47e-05%	1,179,962

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: DHX32
Protein: p.Val352fs
Coding: c.1053dup
MANE Select: NM_018180
dbSNP: rs2494422492
Type: Duplication
Location: chr10:125853999 (GRCh38)
Gene constraint: LOEUF 0.919 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.34

Full DHX32 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DHX32 p.Val352Ile Uncertain significance ★ ⚠ same residue
DHX32 p.Asp203fs Uncertain significance ★ same type
DHX32 p.Met171fs Uncertain significance ★ same type
DHX32 c.850-7dup Benign ★ 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/dhx32-p-val352fs (accessed [today's date]).

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