Is OCLN p.Arg367His (c.1100G>A) pathogenic?

OCLN p.Arg367His (c.1100G>A) is classified Uncertain significance in OCLN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-26). AlphaMissense: likely benign (0.0641); Ultra-rare (popmax 0.0248%, afr); Associated with Inborn genetic diseases.

What condition is associated with OCLN p.Arg367His (c.1100G>A)?

OCLN p.Arg367His (c.1100G>A) is associated with Inborn genetic diseases (ClinVar).

How common is OCLN p.Arg367His (c.1100G>A) in the general population?

OCLN p.Arg367His (c.1100G>A) is ultra-rare (popmax 0.0248%, afr) (gnomAD).

What do computational predictors say about OCLN p.Arg367His (c.1100G>A)?

AlphaMissense predicts likely benign (score 0.0641) — an in-silico prediction, not a clinical call.

OCLN p.Arg367His

c.1100G>A · VCV3923804

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0641 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0248%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0641	likely benign
REVEL	0.098	moderately benign-leaning
SaProt	LLR -7.37	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 -0.056
Regional constraint	o/e 0.13	constrained · MANE · 34 kb · p 7.4e-28 · regional, not allelic
Overall
CADD	15.35	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 0.0248% African / African-American · 17/68,418 alleles

Filtering AF 0.0158% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.00159% 25/1,572,588 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0248%	4,025
Middle Eastern	0.0168%	5,966
Ashkenazi Jewishnot grpmax-eligible	0.00689%	14,515
Remaining individualsnot grpmax-eligible	0.00325%	30,756
European (non-Finnish)	0.000259%	385,688

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.Arg367His
Coding: c.1100G>A
MANE Select: NM_001205254
Type: single nucleotide variant
Location: chr5:69544966 (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 367: 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.Arg367Cys Uncertain significance ★ ⚠ same residue
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

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-arg367his (accessed [today's date]).

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