Is AGPS p.Glu306fs (c.918_919del) pathogenic?

AGPS p.Glu306fs (c.918919del) is classified Likely pathogenic in AGPS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-24). Very rare (popmax 8.48e-05%, nfe); Associated with rhizomelic chondrodysplasia punctata type 3.

What condition is associated with AGPS p.Glu306fs (c.918_919del)?

AGPS p.Glu306fs (c.918_919del) is associated with rhizomelic chondrodysplasia punctata type 3 (ClinVar).

How common is AGPS p.Glu306fs (c.918_919del) in the general population?

AGPS p.Glu306fs (c.918_919del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Rhizomelic chondrodysplasia punctata inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

AGPS p.Glu306fs

c.918_919del · rs1295954187 · VCV2674965

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

rhizomelic chondrodysplasia punctata type 3

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 LoF-intolerant gene
NMD	predicted	premature termination codon in exon 9 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Overall
CADD	34.0	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,168 alleles

Overall 0.000657% 1/152,092 alleles · very rare

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: AGPS
Protein: p.Glu306fs
Coding: c.918_919del
MANE Select: NM_003659
dbSNP: rs1295954187
Type: Deletion
Location: chr2:177461940 (GRCh38)
Gene constraint: LOEUF 0.408 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.27
Residue 306: a binding site; the fad-binding pcmh-type domain

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

Disease context

rhizomelic chondrodysplasia punctata type 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Rhizomelic chondrodysplasia punctata (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

AGPS c.563-10del Benign ★★ same condition
AGPS c.1286delG Likely pathogenic ★ same condition
AGPS c.557_562+5del Likely pathogenic ★ same condition
AGPS p.Asn272fs Likely pathogenic ★ same condition
AGPS p.Glu346fs Likely pathogenic ★ same condition
AGPS p.Glu520fs Likely pathogenic ★ same condition
AGPS p.Glu306= Likely benign ★ same residue
AGPS p.Thr549del 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/agps-p-glu306fs (accessed [today's date]).

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