Is DHX32 p.Asn299fs (c.896del) pathogenic?

DHX32 p.Asn299fs (c.896del) is classified Uncertain significance in DHX32 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-29). Very rare (popmax 0.00268%, afr).

How common is DHX32 p.Asn299fs (c.896del) in the general population?

DHX32 p.Asn299fs (c.896del) is very rare (popmax 0.00268%, afr) (gnomAD).

DHX32 p.Asn299fs

c.896del · rs764421759 · VCV2415259

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 0.00268%, afr)

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 2.9	GERP -0.15, phastCons 1
Overall
CADD	24.2	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 0.00268% African / African-American · 2/74,764 alleles

Filtering AF 0.00188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.00211% 34/1,613,262 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00268%	37,382
European (non-Finnish)	0.00263%	38,058
Remaining individualsnot grpmax-eligible	0.0016%	62,462

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.Asn299fs
Coding: c.896del
MANE Select: NM_018180
dbSNP: rs764421759
Type: Deletion
Location: chr10:125854157 (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.Asn299Lys Uncertain significance ★ ⚠ same residue
DHX32 p.Asn299Ser Uncertain significance ★ ⚠ same residue
DHX32 p.Val337fs Uncertain significance ★ same type
DHX32 c.849+14_849+17del Likely benign ★ same type
DHX32 c.850-6del Likely benign ★ same type
DHX32 c.850-7del 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-asn299fs (accessed [today's date]).

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