Is TMEM216 p.Val136= (c.408G>T) pathogenic?

TMEM216 p.Val136= (c.408G>T) is classified Likely benign in TMEM216 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-29). Very rare (popmax 0.00167%, amr); Associated with Joubert syndrome.

What condition is associated with TMEM216 p.Val136= (c.408G>T)?

TMEM216 p.Val136= (c.408G>T) is associated with Joubert syndrome (ClinVar).

How common is TMEM216 p.Val136= (c.408G>T) in the general population?

TMEM216 p.Val136= (c.408G>T) is very rare (popmax 0.00167%, amr) (gnomAD).

TMEM216 p.Val136=

c.408G>T · rs911000618 · VCV1616710

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Joubert syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.71 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.3	GERP 0.22, phastCons 1
Overall
CADD	8.024	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,994 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,613,716 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,994
European (non-Finnish)	0.000424%	235,981

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: TMEM216
Protein: p.Val136=
Coding: c.408G>T
MANE Select: NM_001173990
dbSNP: rs911000618
Type: single nucleotide variant
Location: chr11:61397952 (GRCh38)
Gene constraint: LOEUF 1.453 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.18

Full TMEM216 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Similar variants

TMEM216 p.Val136Met Uncertain significance ★★ ⚠ same residue
TMEM216 p.Val136Leu Uncertain significance ★ ⚠ same residue
TMEM216 c.137-1G>A Likely pathogenic ★★ same condition
TMEM216 c.137-2A>G Likely pathogenic ★★ same condition
TMEM216 c.229+1G>A Likely pathogenic ★★ same condition
TMEM216 c.230-2A>G Likely pathogenic ★★ same condition
TMEM216 c.34+2T>C Likely pathogenic ★★ same condition
TMEM216 p.Arg73His 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/tmem216-p-val136 (accessed [today's date]).

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