Is DUT p.Arg216Gln (c.647G>A) pathogenic?

DUT p.Arg216Gln (c.647G>A) is classified Uncertain significance in DUT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-04). AlphaMissense: likely pathogenic (0.8478); Very rare (popmax 0.000593%, nfe); Associated with bone marrow failure and diabetes mellitus syndrome.

What condition is associated with DUT p.Arg216Gln (c.647G>A)?

DUT p.Arg216Gln (c.647G>A) is associated with bone marrow failure and diabetes mellitus syndrome (ClinVar).

How common is DUT p.Arg216Gln (c.647G>A) in the general population?

DUT p.Arg216Gln (c.647G>A) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about DUT p.Arg216Gln (c.647G>A)?

AlphaMissense predicts likely pathogenic (score 0.8478) — an in-silico prediction, not a clinical call.

DUT p.Arg216Gln

c.647G>A · rs911063006 · VCV3068241

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8478 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

bone marrow failure and diabetes mellitus syndrome

Computational evidence

Protein change
AlphaMissense	0.8478	likely pathogenic
REVEL	0.556	indeterminate
SaProt	LLR -14.72	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 5.3, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 11 kb · p 0.68 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000593% European (non-Finnish) · 7/1,179,446 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,612,868 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: DUT
Protein: p.Arg216Gln
Coding: c.647G>A
MANE Select: NM_001025248
dbSNP: rs911063006
Type: single nucleotide variant
Location: chr15:48341530 (GRCh38)
Gene constraint: LOEUF 1.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.51 · 12 PDB
Residue 216: a β-strand

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

Disease context

bone marrow failure and diabetes mellitus syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DUT p.Tyr142Cys Likely pathogenic ★ ⚠ same condition
DUT p.Arg173Trp Uncertain significance ★ ⚠ same condition
DUT p.Ala235Ser Uncertain significance ★ ⚠ same type
DUT p.Asp192His Uncertain significance ★ ⚠ same type
DUT p.Gln219His Uncertain significance ★ ⚠ same type
DUT p.Glu223Lys Uncertain significance ★ ⚠ same type
DUT p.Glu240Lys Uncertain significance ★ ⚠ same type
DUT p.Gly135Ala 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/dut-p-arg216gln (accessed [today's date]).

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