Is GNAS p.Phe140fs (c.420del) pathogenic?

GNAS p.Phe140fs (c.420del) is classified Likely pathogenic in GNAS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-02-05). No gnomAD frequency available for this variant; Associated with GNAS-related disorder.

What condition is associated with GNAS p.Phe140fs (c.420del)?

GNAS p.Phe140fs (c.420del) is associated with GNAS-related disorder (ClinVar).

How common is GNAS p.Phe140fs (c.420del) in the general population?

GNAS p.Phe140fs (c.420del) is no gnomAD frequency available for this variant (gnomAD).

GNAS p.Phe140fs

c.420del · rs2517085749 · VCV3061249

Likely pathogenic No assertion criteria

Classification

Likely 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

GNAS-related disorder

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 5 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.7	GERP 1.9, 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.Phe140fs
Coding: c.420del
MANE Select: NM_000516
dbSNP: rs2517085749
Type: Deletion
Location: chr20:58903777 (GRCh38)
Gene constraint: LOEUF 0.302 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.47 · 200 PDB
Residue 140: the 'disordered' region; the g-alpha domain

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

Disease context

GNAS-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GNAS c.212+1del Likely pathogenic ★ same condition
GNAS p.Pro361fs Likely pathogenic ★ same condition
GNAS c.433delG Likely pathogenic same condition
GNAS p.Asp139_Phe140insTer Pathogenic same condition
GNAS p.111TESE[1] Uncertain significance same condition
GNAS p.Ala436_Pro447del Uncertain significance same condition
GNAS p.Asp579del Uncertain significance same condition
GNAS p.Glu81fs Uncertain significance 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-phe140fs (accessed [today's date]).

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