Is DDX6 p.Ser2Asn (c.5G>A) pathogenic?

DDX6 p.Ser2Asn (c.5G>A) is classified Uncertain significance in DDX6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely benign (0.1783); Absent from gnomAD v4.1.

How common is DDX6 p.Ser2Asn (c.5G>A) in the general population?

DDX6 p.Ser2Asn (c.5G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDX6 p.Ser2Asn (c.5G>A)?

AlphaMissense predicts likely benign (score 0.1783) — an in-silico prediction, not a clinical call.

DDX6 p.Ser2Asn

c.5G>A · VCV4795306

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1783 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1783	likely benign
REVEL	0.253	benign-leaning
SaProt	LLR -7.28	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 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 6,531 bp · p 0.42 · regional, not allelic
Overall
CADD	24.9	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

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: DDX6
Protein: p.Ser2Asn
Coding: c.5G>A
MANE Select: NM_004397
Type: single nucleotide variant
Location: chr11:118786247 (GRCh38)
Gene constraint: LOEUF 0.128 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.89 · 9 PDB
Residue 2: the 'disordered' region

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-ser2asn (accessed [today's date]).

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