Is OCLN p.Pro105Ser (c.313C>T) pathogenic?

OCLN p.Pro105Ser (c.313C>T) is classified Uncertain significance in OCLN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely benign (0.0852); Ultra-rare (popmax 0.015%, amr); Associated with Inborn genetic diseases.

What condition is associated with OCLN p.Pro105Ser (c.313C>T)?

OCLN p.Pro105Ser (c.313C>T) is associated with Inborn genetic diseases (ClinVar).

How common is OCLN p.Pro105Ser (c.313C>T) in the general population?

OCLN p.Pro105Ser (c.313C>T) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about OCLN p.Pro105Ser (c.313C>T)?

AlphaMissense predicts likely benign (score 0.0852) — an in-silico prediction, not a clinical call.

OCLN p.Pro105Ser

c.313C>T · VCV4626649

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0852 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0852	likely benign
REVEL	0.221	benign-leaning
SaProt	LLR -4.02	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 7.7	phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 9,860 bp · p 0.0048 · regional, not allelic
Overall
CADD	21.4	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 0.015% Admixed American · 9/59,984 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.000558% 9/1,613,988 alleles · ultra-rare exomes 8/1,461,890 · genomes 1/152,098 · joint denominator

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.Pro105Ser
Coding: c.313C>T
MANE Select: NM_001205254
Type: single nucleotide variant
Location: chr5:69509403 (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 105: the marvel domain

Full OCLN 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

Similar variants

OCLN p.Ala152Thr Uncertain significance ★★ ⚠ same condition
OCLN p.Gln41Glu Uncertain significance ★★ ⚠ same condition
OCLN p.Ile212Val Uncertain significance ★★ ⚠ same condition
OCLN p.Thr158Ala Uncertain significance ★★ ⚠ same condition
OCLN p.Thr158Ile Uncertain significance ★★ ⚠ same condition
OCLN p.Thr86Met Uncertain significance ★★ ⚠ same condition
OCLN p.Tyr106Asp Uncertain significance ★★ same condition
OCLN p.Tyr120His Uncertain significance ★★ ⚠ 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-pro105ser (accessed [today's date]).

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