Is TMEM237 p.Val147Ile (c.439G>A) pathogenic?

TMEM237 p.Val147Ile (c.439G>A) is classified Conflicting classifications of pathogenicity in TMEM237 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2024-06-12). AlphaMissense: likely benign (0.0897); Ultra-rare (popmax 0.0372%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TMEM237 p.Val147Ile (c.439G>A)?

TMEM237 p.Val147Ile (c.439G>A) is associated with Inborn genetic diseases, Joubert syndrome 14 (ClinVar).

How common is TMEM237 p.Val147Ile (c.439G>A) in the general population?

TMEM237 p.Val147Ile (c.439G>A) is ultra-rare (popmax 0.0372%, nfe) (gnomAD).

What do computational predictors say about TMEM237 p.Val147Ile (c.439G>A)?

AlphaMissense predicts likely benign (score 0.0897) — an in-silico prediction, not a clinical call.

TMEM237 p.Val147Ile

c.439G>A · rs200531617 · VCV286536

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0897 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0372%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0897	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -6.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.027	GERP -0.1, phastCons 0.001
Regional constraint	o/e 0.99	unconstrained · MANE · 19 kb · p 0.88 · regional, not allelic
Overall
CADD	20.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0372% European (non-Finnish) · 439/1,179,832 alleles

Filtering AF 0.0343% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0332%

Overall 0.0297% 480/1,613,784 alleles · ultra-rare exomes 443/1,461,580 · genomes 37/152,204 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0372%	2,688
Middle Eastern	0.0329%	3,042
Admixed American	0.03%	3,334
Remaining individualsnot grpmax-eligible	0.0176%	5,678
African / African-American	0.0107%	9,365
Finnishnot grpmax-eligible	0.00312%	32,009

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.Val147Ile
Coding: c.439G>A
MANE Select: NM_001044385
dbSNP: rs200531617
Type: single nucleotide variant
Location: chr2:201632165 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Joubert syndrome 14

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-val147ile (accessed [today's date]).

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