Is TMEM216 p.Pro98= (c.294A>G) pathogenic?

TMEM216 p.Pro98= (c.294A>G) is classified Uncertain significance in TMEM216 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-01-14). Absent from gnomAD v4.1; Associated with Joubert syndrome 2.

What condition is associated with TMEM216 p.Pro98= (c.294A>G)?

TMEM216 p.Pro98= (c.294A>G) is associated with Joubert syndrome 2 (ClinVar).

How common is TMEM216 p.Pro98= (c.294A>G) in the general population?

TMEM216 p.Pro98= (c.294A>G) is absent from gnomAD v4.1 (gnomAD).

TMEM216 p.Pro98=

c.294A>G · VCV4062336

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Joubert syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7	GERP -5
Overall
CADD	1.951	PHRED · no single calibrated threshold — expert panels disagree

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: TMEM216
Protein: p.Pro98=
Coding: c.294A>G
MANE Select: NM_001173990
Type: single nucleotide variant
Location: chr11:61397838 (GRCh38)
Gene constraint: LOEUF 1.453 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.18

Full TMEM216 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TMEM216 c.137-1G>A Likely pathogenic ★★ same condition
TMEM216 c.137-2A>G Likely pathogenic ★★ same condition
TMEM216 c.229+1G>A Likely pathogenic ★★ same condition
TMEM216 c.229+1G>C Likely pathogenic ★★ same condition
TMEM216 c.230-2A>G Likely pathogenic ★★ same condition
TMEM216 c.34+2T>C Likely pathogenic ★★ same condition
TMEM216 p.Arg73His Pathogenic/Likely pathogenic ★★ same condition
TMEM216 p.Arg73Leu 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/tmem216-p-pro98 (accessed [today's date]).

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