Is DHX37 p.Arg674Trp (c.2020C>T) pathogenic?

DHX37 p.Arg674Trp (c.2020C>T) is classified Likely pathogenic in DHX37 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-07-11). AlphaMissense: likely pathogenic (0.906); Absent from gnomAD v4.1; Associated with DHX37-related disorder.

What condition is associated with DHX37 p.Arg674Trp (c.2020C>T)?

DHX37 p.Arg674Trp (c.2020C>T) is associated with DHX37-related disorder, 46,XY sex reversal 11 (ClinVar).

How common is DHX37 p.Arg674Trp (c.2020C>T) in the general population?

DHX37 p.Arg674Trp (c.2020C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DHX37 p.Arg674Trp (c.2020C>T)?

AlphaMissense predicts likely pathogenic (score 0.906) — an in-silico prediction, not a clinical call.

DHX37 p.Arg674Trp

c.2020C>T · rs1954336272 · VCV869421

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.906 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DHX37-related disorder

Computational evidence

Protein change
AlphaMissense	0.906	likely pathogenic ✓ concordant with ClinVar
REVEL	0.913	moderately pathogenic-leaning
SaProt	LLR -15.39	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 0.98, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 180 bp · p 1.8e-07 · regional, not allelic
Overall
CADD	32.0	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: DHX37
Protein: p.Arg674Trp
Coding: c.2020C>T
MANE Select: NM_032656
dbSNP: rs1954336272
Type: single nucleotide variant
Location: chr12:124964419 (GRCh38)
Gene constraint: LOEUF 0.518 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 76.27 · 1 PDB
Residue 674: the helicase c-terminal domain; a UniProt-annotated variant site (in srxy11)

Full DHX37 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DHX37-related disorder

Also linked: 46,XY sex reversal 11

Similar variants

DHX37 p.Arg674Gln Likely pathogenic ★ same residue
DHX37 p.Arg308Gln Pathogenic ★★ same condition
DHX37 p.Ala469Ser Uncertain significance ★★ ⚠ same condition
DHX37 p.Arg151Trp Uncertain significance ★★ ⚠ same condition
DHX37 p.Ile721Thr Uncertain significance ★★ ⚠ same condition
DHX37 p.Pro610Leu Uncertain significance ★★ ⚠ same condition
DHX37 p.Val971Ile Uncertain significance ★★ ⚠ same condition
DHX37 p.Val986Met 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-arg674trp (accessed [today's date]).

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