Is TMEM237 p.Thr3= (c.9T>G) pathogenic?

TMEM237 p.Thr3= (c.9T>G) is classified Benign in TMEM237 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 17.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Joubert syndrome 14.

What condition is associated with TMEM237 p.Thr3= (c.9T>G)?

TMEM237 p.Thr3= (c.9T>G) is associated with Joubert syndrome 14 (ClinVar).

TMEM237 p.Thr3=

Q: How common is TMEM237 p.Thr3= (c.9T>G) in the general population?

TMEM237 p.Thr3= (c.9T>G) is common (popmax 17.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.9T>G · rs6736435 · VCV130594

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 17.8%, eas) — too common for a highly-penetrant pathogenic allele

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 -0.056	GERP -2.1, phastCons 0.004
Overall
CADD	5.427	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 17.8% East Asian · 7,092/39,828 alleles

Filtering AF 17.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.3%

Overall 1.33% 20,503/1,544,272 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	17.8%	6
South Asian	5.42%	18
African / African-American	5.37%	19
Middle Eastern	2.53%	39
Remaining individualsnot grpmax-eligible	2.02%	50
Finnishnot grpmax-eligible	1.18%	85
Admixed American	0.647%	155
Amishnot grpmax-eligible	0.548%	182
Ashkenazi Jewishnot grpmax-eligible	0.341%	294
European (non-Finnish)	0.22%	454

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.Thr3=
Coding: c.9T>G
MANE Select: NM_001044385
dbSNP: rs6736435
Type: single nucleotide variant
Location: chr2:201643392 (GRCh38)
Gene constraint: LOEUF 1.318 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.79
Residue 3: 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-thr3 (accessed [today's date]).

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