Is DUSP18 p.Arg78Cys (c.232C>T) pathogenic?

DUSP18 p.Arg78Cys (c.232C>T) is classified Uncertain significance in DUSP18 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-24). AlphaMissense: likely benign (0.0959); Ultra-rare (popmax 0.0538%, nfe).

How common is DUSP18 p.Arg78Cys (c.232C>T) in the general population?

DUSP18 p.Arg78Cys (c.232C>T) is ultra-rare (popmax 0.0538%, nfe) (gnomAD).

What do computational predictors say about DUSP18 p.Arg78Cys (c.232C>T)?

AlphaMissense predicts likely benign (score 0.0959) — an in-silico prediction, not a clinical call.

DUSP18 p.Arg78Cys

c.232C>T · rs199672327 · VCV3086285

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0959 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0538%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0959	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -7.06	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.4	GERP -0.5, phastCons 0.48
Regional constraint	o/e 0.95	unconstrained · MANE · 563 bp · p 0.42 · regional, not allelic
Overall
CADD	20.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0538% European (non-Finnish) · 635/1,180,038 alleles

Filtering AF 0.0503% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0489%

Overall 0.041% 662/1,614,098 alleles · ultra-rare exomes 636/1,461,892 · genomes 26/152,206 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0538%	1,858
Remaining individualsnot grpmax-eligible	0.0336%	2,976
African / African-American	0.004%	24,981
Admixed American	0.00333%	30,002
South Asian	0.0011%	91,088

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.Arg78Cys
Coding: c.232C>T
MANE Select: NM_152511
dbSNP: rs199672327
Type: single nucleotide variant
Location: chr22:30663772 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 92.97 · 1 PDB
Residue 78: 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.Arg138Trp 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

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-arg78cys (accessed [today's date]).

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