Is DUSP18 p.Phe82Ile (c.244T>A) pathogenic?

DUSP18 p.Phe82Ile (c.244T>A) is classified Uncertain significance in DUSP18 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). AlphaMissense: likely benign (0.2855); Ultra-rare (popmax 0.055%, amr).

How common is DUSP18 p.Phe82Ile (c.244T>A) in the general population?

DUSP18 p.Phe82Ile (c.244T>A) is ultra-rare (popmax 0.055%, amr) (gnomAD).

What do computational predictors say about DUSP18 p.Phe82Ile (c.244T>A)?

AlphaMissense predicts likely benign (score 0.2855) — an in-silico prediction, not a clinical call.

DUSP18 p.Phe82Ile

c.244T>A · VCV3505854

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2855 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.055%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2855	likely benign
REVEL	0.651	pathogenic-leaning
SaProt	LLR -10.75	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 0.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 563 bp · p 0.42 · regional, not allelic
Overall
CADD	22.7	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 0.055% Admixed American · 33/60,000 alleles

Filtering AF 0.0402% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0351%

Overall 0.00235% 38/1,614,110 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.055%	1,818
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.000254%	393,349

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.Phe82Ile
Coding: c.244T>A
MANE Select: NM_152511
Type: single nucleotide variant
Location: chr22:30663760 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 92.97 · 1 PDB
Residue 82: the tyrosine-protein phosphatase domain; an α-helix

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-phe82ile (accessed [today's date]).

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