Is DDX6 p.His239Arg (c.716A>G) pathogenic?

DDX6 p.His239Arg (c.716A>G) is classified Uncertain significance in DDX6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely benign (0.0715); Very rare (popmax 0.00223%, eas).

How common is DDX6 p.His239Arg (c.716A>G) in the general population?

DDX6 p.His239Arg (c.716A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DDX6 p.His239Arg (c.716A>G)?

AlphaMissense predicts likely benign (score 0.0715) — an in-silico prediction, not a clinical call.

DDX6 p.His239Arg

c.716A>G · VCV4686218

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0715 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0715	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -8.20	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 39 bp · p 0.73 · regional, not allelic
Overall
CADD	21.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00223% East Asian · 1/44,810 alleles

Overall 6.86e-05% 1/1,458,162 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: DDX6
Protein: p.His239Arg
Coding: c.716A>G
MANE Select: NM_004397
Type: single nucleotide variant
Location: chr11:118763237 (GRCh38)
Gene constraint: LOEUF 0.128 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.89 · 9 PDB
Residue 239: the helicase atp-binding domain

Full DDX6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDX6 p.Arg396Gln Pathogenic/Likely pathogenic ★★ same type
DDX6 p.Arg319His Uncertain significance ★★ ⚠ same type
DDX6 p.Asn342Asp Uncertain significance ★★ same type
DDX6 p.Gln452Arg Uncertain significance ★★ ⚠ same type
DDX6 p.Lys189Arg Uncertain significance ★★ ⚠ same type
DDX6 p.Pro483Leu Uncertain significance ★★ ⚠ same type
DDX6 p.Tyr296Ter Uncertain significance ★★ same type
DDX6 c.1277-13G>A 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/ddx6-p-his239arg (accessed [today's date]).

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