Is DUSP8 p.Asn192Ser (c.575A>G) pathogenic?

DUSP8 p.Asn192Ser (c.575A>G) is classified Uncertain significance in DUSP8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: likely pathogenic (0.856); Very rare (popmax 8.48e-05%, nfe).

How common is DUSP8 p.Asn192Ser (c.575A>G) in the general population?

DUSP8 p.Asn192Ser (c.575A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about DUSP8 p.Asn192Ser (c.575A>G)?

AlphaMissense predicts likely pathogenic (score 0.856) — an in-silico prediction, not a clinical call.

DUSP8 p.Asn192Ser

c.575A>G · VCV4245619

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.856 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.856	likely pathogenic
REVEL	0.665	pathogenic-leaning
SaProt	LLR -9.69	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 8,318 bp · p 5.2e-15 · regional, not allelic
Overall
CADD	27.0	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 8.48e-05% European (non-Finnish) · 1/1,179,206 alleles

Overall 6.85e-05% 1/1,459,248 alleles · very rare

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: DUSP8
Protein: p.Asn192Ser
Coding: c.575A>G
MANE Select: NM_004420
Type: single nucleotide variant
Location: chr11:1558234 (GRCh38)
Gene constraint: LOEUF 0.813 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 63.99 · 1 PDB
Residue 192: a β-strand; the tyrosine-protein phosphatase domain

Full DUSP8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP8 p.Asp271= Benign ★★ same type
DUSP8 p.Ala101Thr Uncertain significance ★ ⚠ same type
DUSP8 p.Ala272Ser Uncertain significance ★ ⚠ same type
DUSP8 p.Ala305Thr Uncertain significance ★ ⚠ same type
DUSP8 p.Ala325Pro Uncertain significance ★ ⚠ same type
DUSP8 p.Ala345Val Uncertain significance ★ ⚠ same type
DUSP8 p.Ala366Val Uncertain significance ★ ⚠ same type
DUSP8 p.Ala403Val 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/dusp8-p-asn192ser (accessed [today's date]).

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