Is DHX34 p.Ala429Val (c.1286C>T) pathogenic?

DHX34 p.Ala429Val (c.1286C>T) is classified Uncertain significance in DHX34 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely benign (0.1296); Very rare (popmax 0.000424%, nfe).

How common is DHX34 p.Ala429Val (c.1286C>T) in the general population?

DHX34 p.Ala429Val (c.1286C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about DHX34 p.Ala429Val (c.1286C>T)?

AlphaMissense predicts likely benign (score 0.1296) — an in-silico prediction, not a clinical call.

DHX34 p.Ala429Val

c.1286C>T · rs2514954786 · VCV3082211

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1296 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1296	likely benign
REVEL	0.558	indeterminate
SaProt	LLR -11.13	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 29 kb · p 0.62 · regional, not allelic
Overall
CADD	26.9	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 0.000424% European (non-Finnish) · 5/1,179,990 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,850 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.Ala429Val
Coding: c.1286C>T
MANE Select: NM_014681
dbSNP: rs2514954786
Type: single nucleotide variant
Location: chr19:47359981 (GRCh38)
Gene constraint: LOEUF 1.047 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.85
Residue 429: a UniProt-annotated variant site (found in a patient with a neurodevelopmental disorder; uncertain significance); the helicase c-terminal domain

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-ala429val (accessed [today's date]).

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