Is DHX32 p.Leu375= (c.1125C>T) pathogenic?

DHX32 p.Leu375= (c.1125C>T) is classified Likely benign in DHX32 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). Very rare (popmax 0.00407%, nfe).

How common is DHX32 p.Leu375= (c.1125C>T) in the general population?

DHX32 p.Leu375= (c.1125C>T) is very rare (popmax 0.00407%, nfe) (gnomAD).

DHX32 p.Leu375=

c.1125C>T · rs1320735651 · VCV2117554

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00407%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -5.2	GERP -3.2
Overall
CADD	0.951	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00407% European (non-Finnish) · 48/1,179,694 alleles

Filtering AF 0.00315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00279%

Overall 0.0031% 50/1,612,610 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00407%	24,577
African / African-American	0.00134%	74,764
South Asian	0.0011%	90,738

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.Leu375=
Coding: c.1125C>T
MANE Select: NM_078468 · reported on NM_018180
dbSNP: rs1320735651
Type: single nucleotide variant
Location: chr10:125852610 (GRCh38)

Full DHX32 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/dhx32-p-leu375 (accessed [today's date]).

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