Is DUSP8 p.Asp12Glu (c.36T>G) pathogenic?

DUSP8 p.Asp12Glu (c.36T>G) is classified Uncertain significance in DUSP8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-19). AlphaMissense: ambiguous (0.3541); Rare (popmax 0.284%, mid).

How common is DUSP8 p.Asp12Glu (c.36T>G) in the general population?

DUSP8 p.Asp12Glu (c.36T>G) is rare (popmax 0.284%, mid) (gnomAD).

What do computational predictors say about DUSP8 p.Asp12Glu (c.36T>G)?

AlphaMissense predicts ambiguous (score 0.3541) — an in-silico prediction, not a clinical call.

DUSP8 p.Asp12Glu

c.36T>G · rs138137110 · VCV2352176

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3541 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.284%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3541	ambiguous
REVEL	0.196	benign-leaning
SaProt	LLR -3.55	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.6
Regional constraint	o/e 0.61	unconstrained · MANE · 8,318 bp · p 5.2e-15 · regional, not allelic
Overall
CADD	0.047	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 0.284% Middle Eastern · 15/5,282 alleles

Filtering AF 0.175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.141%

Overall 0.0479% 771/1,609,822 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.284%	352
Admixed American	0.0667%	1,500
European (non-Finnish)	0.0575%	1,741
Remaining individualsnot grpmax-eligible	0.0369%	2,710
South Asian	0.0121%	8,271
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,782
African / African-American	0.004%	24,985

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.Asp12Glu
Coding: c.36T>G
MANE Select: NM_004420
dbSNP: rs138137110
Type: single nucleotide variant
Location: chr11:1565791 (GRCh38)
Gene constraint: LOEUF 0.813 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 63.99 · 1 PDB

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-asp12glu (accessed [today's date]).

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