Is DHX34 p.Pro642Ser (c.1924C>T) pathogenic?

DHX34 p.Pro642Ser (c.1924C>T) is classified Uncertain significance in DHX34 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-24). AlphaMissense: ambiguous (0.3657); Very rare (popmax 0.00133%, afr).

How common is DHX34 p.Pro642Ser (c.1924C>T) in the general population?

DHX34 p.Pro642Ser (c.1924C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about DHX34 p.Pro642Ser (c.1924C>T)?

AlphaMissense predicts ambiguous (score 0.3657) — an in-silico prediction, not a clinical call.

DHX34 p.Pro642Ser

c.1924C>T · VCV3839859

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3657 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
AlphaMissense	0.3657	ambiguous
REVEL	0.383	indeterminate
SaProt	LLR -12.36	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 29 kb · p 0.62 · regional, not allelic
Overall
CADD	25.4	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

Grpmax group 0.00133% African / African-American · 1/75,024 alleles

Overall 6.87e-05% 1/1,456,178 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: DHX34
Protein: p.Pro642Ser
Coding: c.1924C>T
MANE Select: NM_014681
Type: single nucleotide variant
Location: chr19:47372885 (GRCh38)
Gene constraint: LOEUF 1.047 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.85
Residue 642: a UniProt-annotated variant site (found in a patient with a neurodevelopmental disorder; uncertain significance)

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

Similar variants

DHX34 p.Pro642Leu Uncertain significance ★ ⚠ same residue
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

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-pro642ser (accessed [today's date]).

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