Is DUSP6 p.Cys39Ter (c.117C>A) pathogenic?

DUSP6 p.Cys39Ter (c.117C>A) is classified Pathogenic in DUSP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-05). Absent from gnomAD v4.1; Associated with hypogonadotropic hypogonadism 19 with or without anosmia.

What condition is associated with DUSP6 p.Cys39Ter (c.117C>A)?

DUSP6 p.Cys39Ter (c.117C>A) is associated with hypogonadotropic hypogonadism 19 with or without anosmia (ClinVar).

How common is DUSP6 p.Cys39Ter (c.117C>A) in the general population?

DUSP6 p.Cys39Ter (c.117C>A) is absent from gnomAD v4.1 (gnomAD).

DUSP6 p.Cys39Ter

c.117C>A · rs1879213059 · VCV1033462

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hypogonadotropic hypogonadism 19 with or without anosmia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 1 of 3
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Overall
CADD	42.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DUSP6
Protein: p.Cys39Ter
Coding: c.117C>A
MANE Select: NM_001946
dbSNP: rs1879213059
Type: single nucleotide variant
Location: chr12:89351923 (GRCh38)
Gene constraint: LOEUF 0.45 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 76.13 · 2 PDB
Residue 39: the rhodanese domain

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

Disease context

hypogonadotropic hypogonadism 19 with or without anosmia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DUSP6 p.Ala57Thr Uncertain significance ★★ ⚠ same condition
DUSP6 p.Phe77Ile Uncertain significance ★★ ⚠ same condition
DUSP6 p.Val114Leu Benign ★★ ⚠ same condition
DUSP6 p.Asn189Ser Conflicting classifications of pathogenicity ★ ⚠ same condition
DUSP6 p.Ser182Phe Conflicting classifications of pathogenicity ★ ⚠ same condition
DUSP6 p.Ala141Asp Uncertain significance ★★ ⚠ same type
DUSP6 p.Asp93Glu Uncertain significance ★★ ⚠ same type
DUSP6 p.Glu32Lys 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/dusp6-p-cys39ter (accessed [today's date]).

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