Is DUSP4 p.Glu6Lys (c.16G>A) pathogenic?

DUSP4 p.Glu6Lys (c.16G>A) is classified Uncertain significance in DUSP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-25). AlphaMissense: ambiguous (0.3477); Very rare (popmax 0.00911%, sas).

How common is DUSP4 p.Glu6Lys (c.16G>A) in the general population?

DUSP4 p.Glu6Lys (c.16G>A) is very rare (popmax 0.00911%, sas) (gnomAD).

What do computational predictors say about DUSP4 p.Glu6Lys (c.16G>A)?

AlphaMissense predicts ambiguous (score 0.3477) — an in-silico prediction, not a clinical call.

DUSP4 p.Glu6Lys

c.16G>A · VCV3842937

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3477 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00911%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3477	ambiguous
REVEL	0.075	moderately benign-leaning
SaProt	LLR -4.94	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 0.83, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 13 kb · p 0.014 · regional, not allelic
Overall
CADD	22.4	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 0.00911% South Asian · 8/87,854 alleles

Filtering AF 0.00451% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00322%

Overall 0.000695% 11/1,582,110 alleles · very rare exomes 8/1,429,908 · genomes 3/152,202 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00911%	10,982
African / African-American	0.0027%	36,999
Remaining individualsnot grpmax-eligible	0.00164%	61,092

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: DUSP4
Protein: p.Glu6Lys
Coding: c.16G>A
MANE Select: NM_001394
Type: single nucleotide variant
Location: chr8:29350263 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 78.78 · 1 PDB

Full DUSP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP4 p.Ala163Gly Uncertain significance ★ ⚠ same type
DUSP4 p.Ala166Thr Uncertain significance ★ ⚠ same type
DUSP4 p.Ala212Ser Uncertain significance ★ ⚠ same type
DUSP4 p.Ala341Ser Uncertain significance ★ ⚠ same type
DUSP4 p.Arg213Gln Uncertain significance ★ ⚠ same type
DUSP4 p.Arg213Trp Uncertain significance ★ ⚠ same type
DUSP4 p.Arg273His Uncertain significance ★ ⚠ same type
DUSP4 p.Arg313His 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/dusp4-p-glu6lys (accessed [today's date]).

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