Is DHX32 p.Leu416Pro (c.1247T>C) pathogenic?

DHX32 p.Leu416Pro (c.1247T>C) is classified Uncertain significance in DHX32 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-26). AlphaMissense: likely benign (0.2089); Very rare (popmax 8.47e-05%, nfe).

How common is DHX32 p.Leu416Pro (c.1247T>C) in the general population?

DHX32 p.Leu416Pro (c.1247T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DHX32 p.Leu416Pro (c.1247T>C)?

AlphaMissense predicts likely benign (score 0.2089) — an in-silico prediction, not a clinical call.

DHX32 p.Leu416Pro

c.1247T>C · VCV3501577

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2089 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2089	likely benign
REVEL	0.12	moderately benign-leaning
SaProt	LLR -10.12	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 16 kb · p 0.068 · regional, not allelic
Overall
CADD	20.8	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 8.47e-05% European (non-Finnish) · 1/1,180,038 alleles

Overall 6.84e-05% 1/1,461,886 alleles · very rare

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.Leu416Pro
Coding: c.1247T>C
MANE Select: NM_078468 · reported on NM_018180
Type: single nucleotide variant
Location: chr10:125852397 (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-leu416pro (accessed [today's date]).

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