Is DHX37 p.Arg1029Pro (c.3086G>C) pathogenic?

DHX37 p.Arg1029Pro (c.3086G>C) is classified Uncertain significance in DHX37 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-20). AlphaMissense: likely benign (0.2797); Very rare (popmax 0.000514%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DHX37 p.Arg1029Pro (c.3086G>C)?

DHX37 p.Arg1029Pro (c.3086G>C) is associated with Inborn genetic diseases, neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies (ClinVar).

How common is DHX37 p.Arg1029Pro (c.3086G>C) in the general population?

DHX37 p.Arg1029Pro (c.3086G>C) is very rare (popmax 0.000514%, nfe) (gnomAD).

What do computational predictors say about DHX37 p.Arg1029Pro (c.3086G>C)?

AlphaMissense predicts likely benign (score 0.2797) — an in-silico prediction, not a clinical call.

DHX37 p.Arg1029Pro

c.3086G>C · rs765324771 · VCV2599923

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2797 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000514%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2797	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -8.02	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.7	GERP -3.1
Regional constraint	o/e 0.86	unconstrained · MANE · 13 kb · p 0.00031 · regional, not allelic
Overall
CADD	3.957	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 0.000514% European (non-Finnish) · 6/1,168,264 alleles

Filtering AF 0.000185% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.000377% 6/1,591,300 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: DHX37
Protein: p.Arg1029Pro
Coding: c.3086G>C
MANE Select: NM_032656
dbSNP: rs765324771
Type: single nucleotide variant
Location: chr12:124950448 (GRCh38)
Gene constraint: LOEUF 0.518 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 76.27 · 1 PDB
Residue 1029: a turn

Full DHX37 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

Also linked: neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies

Similar variants

DHX37 p.Arg1029Gln Uncertain significance ★ ⚠ same residue
DHX37 p.Ala1142Gly Uncertain significance ★★ ⚠ same condition
DHX37 p.Ala469Ser Uncertain significance ★★ ⚠ same condition
DHX37 p.Ala687Val Uncertain significance ★★ ⚠ same condition
DHX37 p.Ala743Thr Uncertain significance ★★ ⚠ same condition
DHX37 p.Arg1042His Uncertain significance ★★ ⚠ same condition
DHX37 p.Arg1060His Uncertain significance ★★ ⚠ same condition
DHX37 p.Arg1075Cys 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/dhx37-p-arg1029pro (accessed [today's date]).

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