Is OCLN p.Arg4Ser (c.12G>C) pathogenic?

OCLN p.Arg4Ser (c.12G>C) is classified Uncertain significance in OCLN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-15). AlphaMissense: likely pathogenic (0.6984); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with OCLN p.Arg4Ser (c.12G>C)?

OCLN p.Arg4Ser (c.12G>C) is associated with Inborn genetic diseases (ClinVar).

How common is OCLN p.Arg4Ser (c.12G>C) in the general population?

OCLN p.Arg4Ser (c.12G>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about OCLN p.Arg4Ser (c.12G>C)?

AlphaMissense predicts likely pathogenic (score 0.6984) — an in-silico prediction, not a clinical call.

OCLN p.Arg4Ser

c.12G>C · rs1032322032 · VCV2335739

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6984 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6984	likely pathogenic
REVEL	0.452	indeterminate
SaProt	LLR -6.21	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -2.8, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 9,860 bp · p 0.0048 · regional, not allelic
Overall
CADD	22.8	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 0.0011% South Asian · 1/90,960 alleles

Overall 6.21e-05% 1/1,609,520 alleles · very rare exomes 1/1,457,280 · genomes 0/152,240 · 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.Arg4Ser
Coding: c.12G>C
MANE Select: NM_001205254
dbSNP: rs1032322032
Type: single nucleotide variant
Location: chr5:69504256 (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 4: the 'disordered' region

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-arg4ser (accessed [today's date]).

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