Is DHX34 p.Pro430Ser (c.1288C>T) pathogenic?

DHX34 p.Pro430Ser (c.1288C>T) is classified Uncertain significance in DHX34 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-30). AlphaMissense: likely benign (0.2862); Very rare (popmax 0.00167%, amr).

How common is DHX34 p.Pro430Ser (c.1288C>T) in the general population?

DHX34 p.Pro430Ser (c.1288C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DHX34 p.Pro430Ser (c.1288C>T)?

AlphaMissense predicts likely benign (score 0.2862) — an in-silico prediction, not a clinical call.

DHX34 p.Pro430Ser

c.1288C>T · rs750416555 · VCV3082212

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2862 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2862	likely benign
REVEL	0.387	indeterminate
SaProt	LLR -12.14	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 7.5	GERP 2.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 29 kb · p 0.62 · regional, not allelic
Overall
CADD	25.3	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 0.00167% Admixed American · 1/59,990 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000889% 13/1,461,796 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,990
European (non-Finnish)	0.00102%	98,329

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.Pro430Ser
Coding: c.1288C>T
MANE Select: NM_014681
dbSNP: rs750416555
Type: single nucleotide variant
Location: chr19:47359983 (GRCh38)
Gene constraint: LOEUF 1.047 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.85
Residue 430: 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-pro430ser (accessed [today's date]).

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