Is OCLN p.Ser2Pro (c.4T>C) pathogenic?

OCLN p.Ser2Pro (c.4T>C) is classified Uncertain significance in OCLN (ClinVar, Single submitter, 1 submitter; last evaluated 2013-03-04). AlphaMissense: likely benign (0.2458); Very rare (popmax 0.00017%, nfe); Associated with pseudo-TORCH syndrome 1.

What condition is associated with OCLN p.Ser2Pro (c.4T>C)?

OCLN p.Ser2Pro (c.4T>C) is associated with pseudo-TORCH syndrome 1 (ClinVar).

How common is OCLN p.Ser2Pro (c.4T>C) in the general population?

OCLN p.Ser2Pro (c.4T>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about OCLN p.Ser2Pro (c.4T>C)?

AlphaMissense predicts likely benign (score 0.2458) — an in-silico prediction, not a clinical call.

OCLN p.Ser2Pro

c.4T>C · rs113706384 · VCV159461

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2458 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

pseudo-TORCH syndrome 1

Computational evidence

Protein change
AlphaMissense	0.2458	likely benign
REVEL	0.394	indeterminate
SaProt	LLR -7.59	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 9,860 bp · p 0.0048 · regional, not allelic
Overall
CADD	26.8	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

Grpmax group 0.00017% European (non-Finnish) · 2/1,174,960 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,456,280 alleles · very rare

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.Ser2Pro
Coding: c.4T>C
MANE Select: NM_001205254
dbSNP: rs113706384
Type: single nucleotide variant
Location: chr5:69504248 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI 0.02 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.82 · 3 PDB
Residue 2: the 'disordered' region

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 p.Ser2= Likely benign ★ same residue
OCLN c.1037+1G>A Pathogenic/Likely pathogenic ★★ same condition
OCLN p.Arg36Ter 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

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-ser2pro (accessed [today's date]).

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