Is OCLN p.Ser2= (c.6A>G) pathogenic?

OCLN p.Ser2= (c.6A>G) is classified Likely benign in OCLN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-01). Ultra-rare (popmax 0.0217%, amr).

How common is OCLN p.Ser2= (c.6A>G) in the general population?

OCLN p.Ser2= (c.6A>G) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

OCLN p.Ser2=

c.6A>G · VCV3772289

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -5.1
Overall
CADD	5.473	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0217% Admixed American · 13/60,012 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.000961% 14/1,456,792 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0217%	4,616
Remaining individualsnot grpmax-eligible	0.0016%	62,338

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.Ser2=
Coding: c.6A>G
MANE Select: NM_001205254
Type: single nucleotide variant
Location: chr5:69504250 (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 2: the 'disordered' region

Full OCLN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

OCLN p.Ser2Pro Uncertain significance ★ ⚠ same residue
OCLN c.1037+1G>A Pathogenic/Likely pathogenic ★★ same type
OCLN p.Arg36Ter Pathogenic ★★ same type
OCLN p.Ala152Thr Uncertain significance ★★ ⚠ same type
OCLN p.Arg66Leu Uncertain significance ★★ ⚠ same type
OCLN p.Gln211Lys Uncertain significance ★★ ⚠ same type
OCLN p.Gln41Glu Uncertain significance ★★ ⚠ same type
OCLN p.Ile212Val Uncertain significance ★★ ⚠ same type

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-ser2 (accessed [today's date]).

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