Is DUSP6 p.Asp93Glu (c.279C>G) pathogenic?

DUSP6 p.Asp93Glu (c.279C>G) is classified Uncertain significance in DUSP6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-06). AlphaMissense: ambiguous (0.494); Ultra-rare (popmax 0.0823%, mid).

How common is DUSP6 p.Asp93Glu (c.279C>G) in the general population?

DUSP6 p.Asp93Glu (c.279C>G) is ultra-rare (popmax 0.0823%, mid) (gnomAD).

What do computational predictors say about DUSP6 p.Asp93Glu (c.279C>G)?

AlphaMissense predicts ambiguous (score 0.494) — an in-silico prediction, not a clinical call.

DUSP6 p.Asp93Glu

c.279C>G · rs370311640 · VCV2260847

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.494 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0823%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.494	ambiguous
REVEL	0.206	benign-leaning
SaProt	LLR -6.40	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 1.6	GERP -1.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 1,392 bp · p 0.98 · regional, not allelic
Overall
CADD	19.01	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 0.0823% Middle Eastern · 5/6,076 alleles

Filtering AF 0.0323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.00771% 124/1,608,502 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0823%	1,215
Admixed American	0.0253%	3,958
European (non-Finnish)	0.0084%	11,902
Remaining individualsnot grpmax-eligible	0.00803%	12,450

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: DUSP6
Protein: p.Asp93Glu
Coding: c.279C>G
MANE Select: NM_001946
dbSNP: rs370311640
Type: single nucleotide variant
Location: chr12:89351761 (GRCh38)
Gene constraint: LOEUF 0.45 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 76.13 · 2 PDB
Residue 93: the rhodanese domain

Full DUSP6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP6 p.Ala141Asp Uncertain significance ★★ ⚠ same type
DUSP6 p.Ala57Thr Uncertain significance ★★ ⚠ same type
DUSP6 p.Glu32Lys Uncertain significance ★★ ⚠ same type
DUSP6 p.Gly30Cys Uncertain significance ★★ ⚠ same type
DUSP6 p.Phe77Ile Uncertain significance ★★ ⚠ same type
DUSP6 c.400+231T>C Benign ★★ same type
DUSP6 c.401-113T>A Benign ★★ same type
DUSP6 c.401-214G>A Benign ★★ 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/dusp6-p-asp93glu (accessed [today's date]).

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