Is DUSP18 p.Arg138Trp (c.412C>T) pathogenic?

DUSP18 p.Arg138Trp (c.412C>T) is classified Uncertain significance in DUSP18 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: likely pathogenic (0.6944); Ultra-rare (popmax 0.0713%, eas).

How common is DUSP18 p.Arg138Trp (c.412C>T) in the general population?

DUSP18 p.Arg138Trp (c.412C>T) is ultra-rare (popmax 0.0713%, eas) (gnomAD).

What do computational predictors say about DUSP18 p.Arg138Trp (c.412C>T)?

AlphaMissense predicts likely pathogenic (score 0.6944) — an in-silico prediction, not a clinical call.

DUSP18 p.Arg138Trp

c.412C>T · rs754173853 · VCV3086286

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6944 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0713%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6944	likely pathogenic
REVEL	0.784	moderately pathogenic-leaning
SaProt	LLR -11.17	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 0.24, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 563 bp · p 0.42 · regional, not allelic
Overall
CADD	29.5	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 0.0713% East Asian · 32/44,886 alleles

Filtering AF 0.0519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0452%

Overall 0.00291% 47/1,614,202 alleles · ultra-rare exomes 38/1,461,892 · genomes 9/152,310 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0713%	1,403
Remaining individualsnot grpmax-eligible	0.0064%	15,627
South Asian	0.00329%	30,362
African / African-American	0.00133%	75,038
European (non-Finnish)	0.000593%	168,578

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: DUSP18
Protein: p.Arg138Trp
Coding: c.412C>T
MANE Select: NM_152511
dbSNP: rs754173853
Type: single nucleotide variant
Location: chr22:30663592 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 92.97 · 1 PDB
Residue 138: the tyrosine-protein phosphatase domain

Full DUSP18 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP18 p.Ala124Thr Uncertain significance ★ ⚠ same type
DUSP18 p.Ala130Val Uncertain significance ★ ⚠ same type
DUSP18 p.Ala7Ser Uncertain significance ★ ⚠ same type
DUSP18 p.Arg13Gln Uncertain significance ★ ⚠ same type
DUSP18 p.Arg13Trp Uncertain significance ★ ⚠ same type
DUSP18 p.Arg142Gln Uncertain significance ★ ⚠ same type
DUSP18 p.Arg183Cys Uncertain significance ★ ⚠ same type
DUSP18 p.Arg78Cys 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/dusp18-p-arg138trp (accessed [today's date]).

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