Is DHX37 p.Pro779Ser (c.2335C>T) pathogenic?

DHX37 p.Pro779Ser (c.2335C>T) is classified Uncertain significance in DHX37 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-02). AlphaMissense: likely pathogenic (0.7289); Absent from gnomAD v4.1.

How common is DHX37 p.Pro779Ser (c.2335C>T) in the general population?

DHX37 p.Pro779Ser (c.2335C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DHX37 p.Pro779Ser (c.2335C>T)?

AlphaMissense predicts likely pathogenic (score 0.7289) — an in-silico prediction, not a clinical call.

DHX37 p.Pro779Ser

c.2335C>T · rs2547113525 · VCV2755225

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7289 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7289	likely pathogenic
REVEL	0.778	moderately pathogenic-leaning
SaProt	LLR -11.68	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 13 kb · p 0.00031 · regional, not allelic
Overall
CADD	25.0	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

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.Pro779Ser
Coding: c.2335C>T
MANE Select: NM_032656
dbSNP: rs2547113525
Type: single nucleotide variant
Location: chr12:124956809 (GRCh38)
Gene constraint: LOEUF 0.518 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 76.27 · 1 PDB
Residue 779: a β-strand

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

Similar variants

DHX37 p.Pro779= Likely benign ★ same residue
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

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-pro779ser (accessed [today's date]).

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