Is OCLN p.Arg36Ter (c.106C>T) pathogenic?

OCLN p.Arg36Ter (c.106C>T) is classified Pathogenic in OCLN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-01-06). Ultra-rare (popmax 0.0133%, amr); Associated with pseudo-TORCH syndrome 1.

What condition is associated with OCLN p.Arg36Ter (c.106C>T)?

OCLN p.Arg36Ter (c.106C>T) is associated with pseudo-TORCH syndrome 1 (ClinVar).

How common is OCLN p.Arg36Ter (c.106C>T) in the general population?

OCLN p.Arg36Ter (c.106C>T) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

OCLN p.Arg36Ter

c.106C>T · rs373915080 · VCV1029457

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Conditions

pseudo-TORCH syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 9
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 2.5, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% Admixed American · 8/60,022 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.00118% 19/1,614,090 alleles · ultra-rare exomes 15/1,461,764 · genomes 4/152,326 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,503
African / African-American	0.00533%	18,765
Remaining individualsnot grpmax-eligible	0.0048%	20,831
South Asian	0.0011%	91,086
European (non-Finnish)	0.000254%	393,312

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: OCLN
Protein: p.Arg36Ter
Coding: c.106C>T
MANE Select: NM_001205254
dbSNP: rs373915080
Type: single nucleotide variant
Location: chr5:69509196 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI 0.02 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.82 · 3 PDB

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

Disease context

pseudo-TORCH syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OCLN c.1037+1G>A Pathogenic/Likely pathogenic ★★ same condition
OCLN p.Thr158Ala Uncertain significance ★★ ⚠ same condition
OCLN p.Thr59Pro Uncertain significance ★★ ⚠ same condition
OCLN p.Pro24Ala Benign/Likely benign ★★ same condition
OCLN c.1037+5G>A Pathogenic ★ same condition
OCLN c.1254-1G>A Likely pathogenic ★ same condition
OCLN c.50+2T>C Likely pathogenic ★ same condition
OCLN p.Glu442Ter 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/ocln-p-arg36ter (accessed [today's date]).

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