Is DHX32 p.Asp445Val (c.1334A>T) pathogenic?

DHX32 p.Asp445Val (c.1334A>T) is classified Uncertain significance in DHX32 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-30). AlphaMissense: likely benign (0.172); Very rare (popmax 0.000169%, nfe).

How common is DHX32 p.Asp445Val (c.1334A>T) in the general population?

DHX32 p.Asp445Val (c.1334A>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about DHX32 p.Asp445Val (c.1334A>T)?

AlphaMissense predicts likely benign (score 0.172) — an in-silico prediction, not a clinical call.

DHX32 p.Asp445Val

c.1334A>T · rs1421365967 · VCV2097161

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.172 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.172	likely benign
REVEL	0.236	benign-leaning
SaProt	LLR -5.71	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 16 kb · p 0.068 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,020 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,014 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.Asp445Val
Coding: c.1334A>T
MANE Select: NM_078468 · reported on NM_018180
dbSNP: rs1421365967
Type: single nucleotide variant
Location: chr10:125852310 (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-asp445val (accessed [today's date]).

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