Is DUSP8 p.Asn388His (c.1162A>C) pathogenic?

DUSP8 p.Asn388His (c.1162A>C) is classified Uncertain significance in DUSP8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: likely benign (0.1245); Ultra-rare (popmax 0.0419%, nfe).

How common is DUSP8 p.Asn388His (c.1162A>C) in the general population?

DUSP8 p.Asn388His (c.1162A>C) is ultra-rare (popmax 0.0419%, nfe) (gnomAD).

What do computational predictors say about DUSP8 p.Asn388His (c.1162A>C)?

AlphaMissense predicts likely benign (score 0.1245) — an in-silico prediction, not a clinical call.

DUSP8 p.Asn388His

c.1162A>C · VCV4245614

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1245 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0419%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1245	likely benign
REVEL	0.182	moderately benign-leaning
SaProt	LLR -5.95	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 7.4	phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 861 bp · p 0.038 · regional, not allelic
Overall
CADD	25.1	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

Grpmax group 0.0419% European (non-Finnish) · 466/1,113,072 alleles

Filtering AF 0.0387% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0374%

Overall 0.0346% 513/1,482,882 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0419%	2,389
Remaining individualsnot grpmax-eligible	0.0333%	3,001
Ashkenazi Jewishnot grpmax-eligible	0.0187%	5,359
South Asian	0.0151%	6,636
African / African-American	0.0133%	7,538
East Asian	0.00578%	17,287

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.Asn388His
Coding: c.1162A>C
MANE Select: NM_004420
Type: single nucleotide variant
Location: chr11:1557234 (GRCh38)
Gene constraint: LOEUF 0.813 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 63.99 · 1 PDB
Residue 388: the 'disordered' region

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-asn388his (accessed [today's date]).

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