Is DUSP13B p.Arg333Trp (c.997C>T) pathogenic?

DUSP13B p.Arg333Trp (c.997C>T) is classified Uncertain significance in DUSP13B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-25). AlphaMissense: likely benign (0.1723); Ultra-rare (popmax 0.0337%, mid).

How common is DUSP13B p.Arg333Trp (c.997C>T) in the general population?

DUSP13B p.Arg333Trp (c.997C>T) is ultra-rare (popmax 0.0337%, mid) (gnomAD).

What do computational predictors say about DUSP13B p.Arg333Trp (c.997C>T)?

AlphaMissense predicts likely benign (score 0.1723) — an in-silico prediction, not a clinical call.

DUSP13B p.Arg333Trp

c.997C>T · VCV3505826

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1723 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0337%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1723	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -10.66	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -5, phastCons 0.009
Regional constraint	o/e 1.08	unconstrained · MANE · 937 bp · p 0.38 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R197W vs ClinVar R333W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0337% Middle Eastern · 2/5,930 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00246%

Overall 0.00174% 28/1,613,632 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0337%	2,965
South Asian	0.00549%	18,214
Admixed American	0.005%	19,997
Remaining individualsnot grpmax-eligible	0.0032%	31,224
Finnishnot grpmax-eligible	0.00157%	63,874
European (non-Finnish)	0.00127%	78,668

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: DUSP13B
Protein: p.Arg333Trp
Coding: c.997C>T
MANE Select: NM_001363514
Type: single nucleotide variant
Location: chr10:75094684 (GRCh38)
Structure: AlphaFold pLDDT 90.56 · 2 PDB

Full DUSP13B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP13B p.Arg333Gln Uncertain significance ★ ⚠ same residue
DUSP13B p.Pro161Gln Uncertain significance ★★ ⚠ same type
DUSP13B c.582-1G>T Uncertain significance ★ same type
DUSP13B p.Ala165Thr Uncertain significance ★ ⚠ same type
DUSP13B p.Ala256Asp Uncertain significance ★ ⚠ same type
DUSP13B p.Ala262Gly Uncertain significance ★ ⚠ same type
DUSP13B p.Ala287Asp Uncertain significance ★ ⚠ same type
DUSP13B p.Arg146Gln 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/dusp13b-p-arg333trp (accessed [today's date]).

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