Is DUSP8 p.Asp309Glu (c.927C>G) pathogenic?

DUSP8 p.Asp309Glu (c.927C>G) is classified Uncertain significance in DUSP8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely benign (0.0802); Absent from gnomAD v4.1.

How common is DUSP8 p.Asp309Glu (c.927C>G) in the general population?

DUSP8 p.Asp309Glu (c.927C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUSP8 p.Asp309Glu (c.927C>G)?

AlphaMissense predicts likely benign (score 0.0802) — an in-silico prediction, not a clinical call.

DUSP8 p.Asp309Glu

c.927C>G · VCV4245615

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0802 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,564,774)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0802	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -5.39	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 -3.9
Regional constraint	o/e 1.10	unconstrained · MANE · 861 bp · p 0.038 · regional, not allelic
Overall
CADD	0.312	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

No allele count reported in gnomAD v4.1 (AN 1,564,774). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DUSP8
Protein: p.Asp309Glu
Coding: c.927C>G
MANE Select: NM_004420
Type: single nucleotide variant
Location: chr11:1557469 (GRCh38)
Gene constraint: LOEUF 0.813 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 63.99 · 1 PDB
Residue 309: the 'disordered' region

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

Similar variants

DUSP8 p.Asp309Ala Uncertain significance ★ ⚠ same residue
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

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-asp309glu (accessed [today's date]).

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