Is DHX9 p.Pro703Gln (c.2108C>A) pathogenic?

DHX9 p.Pro703Gln (c.2108C>A) is classified Uncertain significance in DHX9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely benign (0.1559); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DHX9 p.Pro703Gln (c.2108C>A)?

DHX9 p.Pro703Gln (c.2108C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DHX9 p.Pro703Gln (c.2108C>A) in the general population?

DHX9 p.Pro703Gln (c.2108C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DHX9 p.Pro703Gln (c.2108C>A)?

AlphaMissense predicts likely benign (score 0.1559) — an in-silico prediction, not a clinical call.

DHX9 p.Pro703Gln

c.2108C>A · VCV4240425

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1559 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1559	likely benign
REVEL	0.259	benign-leaning
SaProt	LLR -10.42	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 4,180 bp · p 1.3e-09 · regional, not allelic
Overall
CADD	26.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DHX9
Protein: p.Pro703Gln
Coding: c.2108C>A
MANE Select: NM_001357
Type: single nucleotide variant
Location: chr1:182876525 (GRCh38)
Gene constraint: LOEUF 0.263 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.84 · 7 PDB
Residue 703: the 'necessary for interaction with h2ax' region; the 'core helicase' region; an α-helix; the helicase c-terminal domain; a UniProt-annotated variant site (in mrd75; likely pathogenic)

Full DHX9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DHX9 p.Pro586Ala Uncertain significance ★★ ⚠ same condition
DHX9 p.Arg1052Ter Pathogenic ★ same condition
DHX9 p.Arg764Ter Pathogenic ★ same condition
DHX9 p.Arg767Ter Pathogenic ★ same condition
DHX9 p.Tyr568Ter Pathogenic ★ same condition
DHX9 c.3260+5G>A Uncertain significance ★ same condition
DHX9 p.Ala1106Thr Uncertain significance ★ ⚠ same condition
DHX9 p.Ala1165Thr Uncertain significance ★ ⚠ same condition

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/dhx9-p-pro703gln (accessed [today's date]).

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