Is DHX34 p.Arg1139Pro (c.3416G>C) pathogenic?

DHX34 p.Arg1139Pro (c.3416G>C) is classified Uncertain significance in DHX34 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-29). AlphaMissense: likely pathogenic (0.8532); Absent from gnomAD v4.1.

How common is DHX34 p.Arg1139Pro (c.3416G>C) in the general population?

DHX34 p.Arg1139Pro (c.3416G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DHX34 p.Arg1139Pro (c.3416G>C)?

AlphaMissense predicts likely pathogenic (score 0.8532) — an in-silico prediction, not a clinical call.

DHX34 p.Arg1139Pro

c.3416G>C · rs763413315 · VCV3082236

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8532 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8532	likely pathogenic
REVEL	0.096	moderately benign-leaning
SaProt	LLR -14.15	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 29 kb · p 0.62 · regional, not allelic
Overall
CADD	22.6	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: DHX34
Protein: p.Arg1139Pro
Coding: c.3416G>C
MANE Select: NM_014681
dbSNP: rs763413315
Type: single nucleotide variant
Location: chr19:47382097 (GRCh38)
Gene constraint: LOEUF 1.047 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.85
Residue 1139: a UniProt-annotated variant site (found in a patient with a neurodevelopmental disorder; uncertain significance); the 'required for phosphorylation of upf1. not required for interaction with upf1' region; the 'required for the interaction with smg1 and subsequent phosphorylation of upf1' region

Full DHX34 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DHX34 p.Asn682Thr Uncertain significance ★★ ⚠ same type
DHX34 p.Ser624Arg Uncertain significance ★★ ⚠ same type
DHX34 p.Thr973Met Uncertain significance ★★ ⚠ same type
DHX34 c.3299-3T>C Benign ★★ same type
DHX34 c.3299-6C>T Likely benign ★★ same type
DHX34 p.Ala127Val Likely benign ★★ ⚠ same type
DHX34 p.Ala416Thr Benign/Likely benign ★★ same type
DHX34 p.Ala817Thr Benign ★★ 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/dhx34-p-arg1139pro (accessed [today's date]).

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