Is OCLN p.Pro291Ser (c.871C>T) pathogenic?

OCLN p.Pro291Ser (c.871C>T) is classified Conflicting classifications of pathogenicity in OCLN (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-02-24). AlphaMissense: likely benign (0.129); Ultra-rare (popmax 0.0493%, mid); Associated with Inborn genetic diseases.

What condition is associated with OCLN p.Pro291Ser (c.871C>T)?

OCLN p.Pro291Ser (c.871C>T) is associated with Inborn genetic diseases (ClinVar).

How common is OCLN p.Pro291Ser (c.871C>T) in the general population?

OCLN p.Pro291Ser (c.871C>T) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

What do computational predictors say about OCLN p.Pro291Ser (c.871C>T)?

AlphaMissense predicts likely benign (score 0.129) — an in-silico prediction, not a clinical call.

OCLN p.Pro291Ser

c.871C>T · rs373344533 · VCV1399388

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.129 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.129	likely benign
REVEL	0.196	benign-leaning
SaProt	LLR -6.68	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 1.4	GERP 0.011, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 9,860 bp · p 0.0048 · regional, not allelic
Overall
CADD	16.83	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 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00812%

Overall 0.00979% 158/1,613,708 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
Ashkenazi Jewishnot grpmax-eligible	0.0405%	2,466
Remaining individualsnot grpmax-eligible	0.016%	6,247
Finnishnot grpmax-eligible	0.0141%	7,112
European (non-Finnish)	0.0102%	9,832
Admixed American	0.00667%	14,999

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.Pro291Ser
Coding: c.871C>T
MANE Select: NM_001205254
dbSNP: rs373344533
Type: single nucleotide variant
Location: chr5:69514089 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI 0.02 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.82 · 3 PDB

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-pro291ser (accessed [today's date]).

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