Is DHX37 p.Arg892Trp (c.2674C>T) pathogenic?

DHX37 p.Arg892Trp (c.2674C>T) is classified Uncertain significance in DHX37 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-11). AlphaMissense: likely pathogenic (0.6059); Ultra-rare (popmax 0.01%, amr).

How common is DHX37 p.Arg892Trp (c.2674C>T) in the general population?

DHX37 p.Arg892Trp (c.2674C>T) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about DHX37 p.Arg892Trp (c.2674C>T)?

AlphaMissense predicts likely pathogenic (score 0.6059) — an in-silico prediction, not a clinical call.

DHX37 p.Arg892Trp

c.2674C>T · rs369049552 · VCV2726543

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6059 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6059	likely pathogenic
REVEL	0.493	indeterminate
SaProt	LLR -15.85	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	GERP 0.72, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 13 kb · p 0.00031 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.01% Admixed American · 6/59,846 alleles

Filtering AF 0.00429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00296%

Overall 0.00254% 41/1,611,432 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,974
Finnishnot grpmax-eligible	0.00477%	20,965
European (non-Finnish)	0.00246%	40,664
East Asian	0.00223%	44,826
Remaining individualsnot grpmax-eligible	0.0016%	62,306
African / African-American	0.00134%	74,902

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.Arg892Trp
Coding: c.2674C>T
MANE Select: NM_032656
dbSNP: rs369049552
Type: single nucleotide variant
Location: chr12:124953901 (GRCh38)
Gene constraint: LOEUF 0.518 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 76.27 · 1 PDB
Residue 892: an α-helix

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

Similar variants

DHX37 p.Arg308Gln Pathogenic ★★ same type
DHX37 p.Arg674Trp Likely pathogenic ★★ same type
DHX37 p.Ala1142Gly Uncertain significance ★★ ⚠ same type
DHX37 p.Ala469Ser Uncertain significance ★★ ⚠ same type
DHX37 p.Ala687Val Uncertain significance ★★ ⚠ same type
DHX37 p.Ala743Thr Uncertain significance ★★ ⚠ same type
DHX37 p.Ala864Ser Uncertain significance ★★ ⚠ same type
DHX37 p.Arg1029Pro Uncertain significance ★★ ⚠ same type

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-arg892trp (accessed [today's date]).

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