Is TMEM237 p.Ser392= (c.1176A>G) pathogenic?

TMEM237 p.Ser392= (c.1176A>G) is classified Likely benign in TMEM237 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-08). Ultra-rare (popmax 0.016%, afr); Associated with Joubert syndrome 14.

What condition is associated with TMEM237 p.Ser392= (c.1176A>G)?

TMEM237 p.Ser392= (c.1176A>G) is associated with Joubert syndrome 14 (ClinVar).

How common is TMEM237 p.Ser392= (c.1176A>G) in the general population?

TMEM237 p.Ser392= (c.1176A>G) is ultra-rare (popmax 0.016%, afr) (gnomAD).

TMEM237 p.Ser392=

c.1176A>G · rs773344011 · VCV741048

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

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 -0.61
Overall
CADD	4.068	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.016% African / African-American · 12/74,910 alleles

Filtering AF 0.00922% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.00093% 15/1,612,068 alleles · ultra-rare exomes 10/1,459,922 · genomes 5/152,146 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,243
European (non-Finnish)	0.000254%	392,969

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.Ser392=
Coding: c.1176A>G
MANE Select: NM_001044385
dbSNP: rs773344011
Type: single nucleotide variant
Location: chr2:201624306 (GRCh38)
Gene constraint: LOEUF 1.318 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.79

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 p.Ser392fs Uncertain significance ★★ same residue
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

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-ser392 (accessed [today's date]).

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