Is DUS2 p.Gln408Pro (c.1223A>C) pathogenic?

DUS2 p.Gln408Pro (c.1223A>C) is classified Uncertain significance in DUS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: ambiguous (0.5242); Absent from gnomAD v4.1.

How common is DUS2 p.Gln408Pro (c.1223A>C) in the general population?

DUS2 p.Gln408Pro (c.1223A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUS2 p.Gln408Pro (c.1223A>C)?

AlphaMissense predicts ambiguous (score 0.5242) — an in-silico prediction, not a clinical call.

DUS2 p.Gln408Pro

c.1223A>C · VCV4662458

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5242 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5242	ambiguous
REVEL	0.634	indeterminate
SaProt	LLR -12.61	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 41 kb · p 0.0097 · regional, not allelic
Overall
CADD	23.7	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

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: DUS2
Protein: p.Gln408Pro
Coding: c.1223A>C
MANE Select: NM_017803
Type: single nucleotide variant
Location: chr16:68078497 (GRCh38)
Gene constraint: LOEUF 0.875 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.81 · 11 PDB
Residue 408: the drbm domain; a β-strand

Full DUS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUS2 p.Ala181Thr Uncertain significance ★ ⚠ same type
DUS2 p.Ala244Gly Uncertain significance ★ ⚠ same type
DUS2 p.Ala271Val Uncertain significance ★ ⚠ same type
DUS2 p.Ala336Thr Uncertain significance ★ ⚠ same type
DUS2 p.Ala346Val Uncertain significance ★ ⚠ same type
DUS2 p.Ala36Val Uncertain significance ★ ⚠ same type
DUS2 p.Ala425Val Uncertain significance ★ ⚠ same type
DUS2 p.Arg101Thr Uncertain significance ★ ⚠ 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/dus2-p-gln408pro (accessed [today's date]).

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