Is DUS2 p.Arg243Gln (c.728G>A) pathogenic?

DUS2 p.Arg243Gln (c.728G>A) is classified Uncertain significance in DUS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-10). AlphaMissense: likely pathogenic (0.8859); Very rare (popmax 0.00667%, afr).

How common is DUS2 p.Arg243Gln (c.728G>A) in the general population?

DUS2 p.Arg243Gln (c.728G>A) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about DUS2 p.Arg243Gln (c.728G>A)?

AlphaMissense predicts likely pathogenic (score 0.8859) — an in-silico prediction, not a clinical call.

DUS2 p.Arg243Gln

c.728G>A · VCV3505774

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8859 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8859	likely pathogenic
REVEL	0.766	pathogenic-leaning
SaProt	LLR -8.77	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 41 kb · p 0.0097 · regional, not allelic
Overall
CADD	28.2	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 0.00667% African / African-American · 5/74,922 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00229% 37/1,614,086 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,984
South Asian	0.00329%	30,361
Remaining individualsnot grpmax-eligible	0.0032%	31,242
European (non-Finnish)	0.0022%	45,386
Admixed American	0.00167%	60,010

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: DUS2
Protein: p.Arg243Gln
Coding: c.728G>A
MANE Select: NM_017803
Type: single nucleotide variant
Location: chr16:68071026 (GRCh38)
Gene constraint: LOEUF 0.875 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.81 · 11 PDB
Residue 243: a binding site; the 'catalytic domain' region; an α-helix

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-arg243gln (accessed [today's date]).

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