Is OCLN p.Ser505Arg (c.1515C>G) pathogenic?

OCLN p.Ser505Arg (c.1515C>G) is classified Uncertain significance in OCLN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-09). AlphaMissense: ambiguous (0.4039); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with OCLN p.Ser505Arg (c.1515C>G)?

OCLN p.Ser505Arg (c.1515C>G) is associated with Inborn genetic diseases (ClinVar).

How common is OCLN p.Ser505Arg (c.1515C>G) in the general population?

OCLN p.Ser505Arg (c.1515C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OCLN p.Ser505Arg (c.1515C>G)?

AlphaMissense predicts ambiguous (score 0.4039) — an in-silico prediction, not a clinical call.

OCLN p.Ser505Arg

c.1515C>G · rs1190173129 · VCV2402545

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4039 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,958)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4039	ambiguous
REVEL	0.222	benign-leaning
SaProt	LLR -4.99	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.84	phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 5,629 bp · p 0.0043 · regional, not allelic
Overall
CADD	22.4	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

No allele count reported in gnomAD v4.1 (AN 1,613,958). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: OCLN
Protein: p.Ser505Arg
Coding: c.1515C>G
MANE Select: NM_001205254
dbSNP: rs1190173129
Type: single nucleotide variant
Location: chr5:69553617 (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 505: the ocel domain; an α-helix

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-ser505arg (accessed [today's date]).

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