Is TMEM237 p.Gly343Ser (c.1027G>A) pathogenic?

TMEM237 p.Gly343Ser (c.1027G>A) is classified Uncertain significance in TMEM237 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-23). AlphaMissense: likely benign (0.0919); No allele count reported in gnomAD v4.1 (AN 1,605,536); Associated with Joubert syndrome 14.

What condition is associated with TMEM237 p.Gly343Ser (c.1027G>A)?

TMEM237 p.Gly343Ser (c.1027G>A) is associated with Joubert syndrome 14 (ClinVar).

How common is TMEM237 p.Gly343Ser (c.1027G>A) in the general population?

TMEM237 p.Gly343Ser (c.1027G>A) is no allele count reported in gnomAD v4.1 (AN 1,605,536) (gnomAD).

What do computational predictors say about TMEM237 p.Gly343Ser (c.1027G>A)?

AlphaMissense predicts likely benign (score 0.0919) — an in-silico prediction, not a clinical call.

TMEM237 p.Gly343Ser

c.1027G>A · rs2469489169 · VCV2116045

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0919 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,605,536)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Joubert syndrome 14

Computational evidence

Protein change
AlphaMissense	0.0919	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -5.21	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.2	phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 19 kb · p 0.88 · regional, not allelic
Overall
CADD	19.71	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,605,536). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TMEM237
Protein: p.Gly343Ser
Coding: c.1027G>A
MANE Select: NM_001044385
dbSNP: rs2469489169
Type: single nucleotide variant
Location: chr2:201627331 (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 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-gly343ser (accessed [today's date]).

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