Is GNAS p.Asp85fs (c.254dup) pathogenic?

GNAS p.Asp85fs (c.254dup) is classified Pathogenic in GNAS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2007-05-01). No gnomAD frequency available for this variant; Associated with pseudohypoparathyroidism.

What condition is associated with GNAS p.Asp85fs (c.254dup)?

GNAS p.Asp85fs (c.254dup) is associated with pseudohypoparathyroidism (ClinVar).

How common is GNAS p.Asp85fs (c.254dup) in the general population?

GNAS p.Asp85fs (c.254dup) is no gnomAD frequency available for this variant (gnomAD).

GNAS p.Asp85fs

c.254dup · rs2146079806 · VCV15957

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

pseudohypoparathyroidism

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 3 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.8	GERP 0.84, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GNAS
Protein: p.Asp85fs
Coding: c.254dup
MANE Select: NM_000516
dbSNP: rs2146079806
Type: Duplication
Location: chr20:58898981 (GRCh38)
Gene constraint: LOEUF 0.302 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.47 · 200 PDB
Residue 85: the 'disordered' region; the g-alpha domain

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

Disease context

pseudohypoparathyroidism — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GNAS p.Phe85Leu Uncertain significance ★ ⚠ same residue
GNAS p.Thr369_Glu370insAlaValAspThr Pathogenic same condition
GNAS p.Asp85Asn Uncertain significance ⚠ same residue
GNAS p.Arg165Cys Pathogenic ★★ same condition
GNAS p.Arg231Cys Pathogenic/Likely pathogenic ★★ same condition
GNAS p.Arg231His Pathogenic ★★ same condition
GNAS p.Asn371fs Pathogenic ★★ same condition
GNAS p.Gln12Ter Pathogenic ★★ same condition

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/gnas-p-asp85fs (accessed [today's date]).

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