Is DUSP22 p.Leu159Phe (c.477G>T) pathogenic?

DUSP22 p.Leu159Phe (c.477G>T) is classified Likely benign in DUSP22 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-09-28). AlphaMissense: likely benign (0.124); Rare (popmax 0.827%, afr); Associated with DUSP22-related disorder.

What condition is associated with DUSP22 p.Leu159Phe (c.477G>T)?

DUSP22 p.Leu159Phe (c.477G>T) is associated with DUSP22-related disorder (ClinVar).

How common is DUSP22 p.Leu159Phe (c.477G>T) in the general population?

DUSP22 p.Leu159Phe (c.477G>T) is rare (popmax 0.827%, afr) (gnomAD).

What do computational predictors say about DUSP22 p.Leu159Phe (c.477G>T)?

AlphaMissense predicts likely benign (score 0.124) — an in-silico prediction, not a clinical call.

DUSP22 p.Leu159Phe

c.477G>T · rs148581187 · VCV3039128

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.124 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.827%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DUSP22-related disorder

Computational evidence

Protein change
AlphaMissense	0.124	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -8.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP -2.2, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 56 kb · p 0.00021 · regional, not allelic
Overall
CADD	17.15	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 0.827% African / African-American · 618/74,772 alleles

Filtering AF 0.773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.751%

Overall 0.0486% 784/1,613,942 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.827%	121
Middle Eastern	0.264%	379
Admixed American	0.0866%	1,154
Remaining individualsnot grpmax-eligible	0.0768%	1,302
European (non-Finnish)	0.00407%	24,584
South Asian	0.0022%	45,546

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: DUSP22
Protein: p.Leu159Phe
Coding: c.477G>T
MANE Select: NM_001286555
dbSNP: rs148581187
Type: single nucleotide variant
Location: chr6:348810 (GRCh38)
Gene constraint: LOEUF 1.407 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.64 · 8 PDB

Full DUSP22 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DUSP22-related disorder

Similar variants

DUSP22 c.189-4C>T Likely benign same condition
DUSP22 c.-5C>T Likely benign same condition
DUSP22 c.*1871C>G Likely benign same condition
DUSP22 c.*1878G>A Benign same condition
DUSP22 c.*2G>A Likely benign same condition
DUSP22 c.*8G>A Likely benign same condition
DUSP22 p.Ala23= Likely benign same condition
DUSP22 p.Ala56= Likely benign same condition

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/dusp22-p-leu159phe (accessed [today's date]).

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