Is TMEM237 p.Pro21fs (c.62del) pathogenic?

TMEM237 p.Pro21fs (c.62del) is classified Pathogenic/Likely pathogenic in TMEM237 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-29). Very rare (popmax 0.00111%, nfe); Associated with Joubert syndrome 14.

What condition is associated with TMEM237 p.Pro21fs (c.62del)?

TMEM237 p.Pro21fs (c.62del) is associated with Joubert syndrome 14, Joubert syndrome (ClinVar).

How common is TMEM237 p.Pro21fs (c.62del) in the general population?

TMEM237 p.Pro21fs (c.62del) is very rare (popmax 0.00111%, nfe) (gnomAD).

TMEM237 p.Pro21fs

c.62del · rs1574587553 · VCV666987

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00111%, nfe)

Conditions

Joubert syndrome 14

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.025	GERP -1.1, phastCons 0.97

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00111% European (non-Finnish) · 13/1,171,454 alleles

Filtering AF 0.000619% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000477%

Overall 0.000812% 13/1,601,932 alleles · very rare exomes 13/1,449,614 · genomes 0/152,318 · joint denominator

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: TMEM237
Protein: p.Pro21fs
Coding: c.62del
MANE Select: NM_001044385
dbSNP: rs1574587553
Type: Deletion
Location: chr2:201640905 (GRCh38)
Gene constraint: LOEUF 1.318 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.79
Residue 21: the 'disordered' region

Full TMEM237 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome 14 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Joubert syndrome

Similar variants

TMEM237 c.869+1del Pathogenic ★★ same condition
TMEM237 p.Ile202fs Pathogenic/Likely pathogenic ★★ same condition
TMEM237 p.400KE[1] Uncertain significance ★★ same condition
TMEM237 p.Ala406fs Uncertain significance ★★ same condition
TMEM237 p.Ser392fs Uncertain significance ★★ same condition
TMEM237 c.678-20_678-17del Benign/Likely benign ★★ same condition
TMEM237 c.870-13_870-12del Benign ★★ same condition
TMEM237 p.Asp149fs Likely 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/tmem237-p-pro21fs (accessed [today's date]).

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