Is TMEM237 p.Ser68= (c.204A>G) pathogenic?

TMEM237 p.Ser68= (c.204A>G) is classified Likely benign in TMEM237 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-01). Absent from gnomAD v4.1; Associated with Joubert syndrome 14.

What condition is associated with TMEM237 p.Ser68= (c.204A>G)?

TMEM237 p.Ser68= (c.204A>G) is associated with Joubert syndrome 14 (ClinVar).

How common is TMEM237 p.Ser68= (c.204A>G) in the general population?

TMEM237 p.Ser68= (c.204A>G) is absent from gnomAD v4.1 (gnomAD).

TMEM237 p.Ser68=

c.204A>G · rs2105902357 · VCV1619566

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Joubert syndrome 14

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 0.026	GERP 0.095, phastCons 0.005
Overall
CADD	8.439	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: TMEM237
Protein: p.Ser68=
Coding: c.204A>G
MANE Select: NM_001044385
dbSNP: rs2105902357
Type: single nucleotide variant
Location: chr2:201636818 (GRCh38)
Gene constraint: LOEUF 1.318 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.79
Residue 68: 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

Similar variants

TMEM237 c.136+1G>T Likely pathogenic ★★ same condition
TMEM237 c.553+1G>A Pathogenic/Likely pathogenic ★★ same condition
TMEM237 c.677+1G>A Pathogenic/Likely pathogenic ★★ same condition
TMEM237 c.869+1G>A Pathogenic/Likely pathogenic ★★ same condition
TMEM237 c.943+1G>T Pathogenic ★★ same condition
TMEM237 p.Arg109Ter Pathogenic ★★ same condition
TMEM237 p.Arg18Ter Pathogenic ★★ same condition
TMEM237 p.Arg301Ter Pathogenic/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-ser68 (accessed [today's date]).

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