Is OCLN p.Pro24Ala (c.70C>G) pathogenic?

OCLN p.Pro24Ala (c.70C>G) is classified Benign/Likely benign in OCLN (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.1233); Low-frequency (popmax 1.18%, nfe); Associated with pseudo-TORCH syndrome 1.

What condition is associated with OCLN p.Pro24Ala (c.70C>G)?

OCLN p.Pro24Ala (c.70C>G) is associated with pseudo-TORCH syndrome 1 (ClinVar).

How common is OCLN p.Pro24Ala (c.70C>G) in the general population?

OCLN p.Pro24Ala (c.70C>G) is low-frequency (popmax 1.18%, nfe) (gnomAD).

What do computational predictors say about OCLN p.Pro24Ala (c.70C>G)?

AlphaMissense predicts likely benign (score 0.1233) — an in-silico prediction, not a clinical call.

OCLN p.Pro24Ala

c.70C>G · rs147125035 · VCV159462

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1233 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.18%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

pseudo-TORCH syndrome 1

Computational evidence

Protein change
AlphaMissense	0.1233	likely benign
REVEL	0.356	indeterminate
SaProt	LLR -6.74	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 9,860 bp · p 0.0048 · regional, not allelic
Overall
CADD	24.9	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 1.18% European (non-Finnish) · 13,900/1,179,784 alleles

Filtering AF 1.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.16%

Overall 1.04% 16,717/1,613,900 alleles · low-frequency exomes 15,434/1,461,594 · genomes 1,283/152,306 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.06%	49
European (non-Finnish)grpmax	1.18%	85
Admixed American	0.821%	122
Remaining individualsnot grpmax-eligible	0.811%	123
Ashkenazi Jewishnot grpmax-eligible	0.598%	167
Middle Eastern	0.297%	337
South Asian	0.208%	482
African / African-American	0.152%	658

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro24Ala
Coding: c.70C>G
MANE Select: NM_001205254
dbSNP: rs147125035
Type: single nucleotide variant
Location: chr5:69509160 (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

pseudo-TORCH syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OCLN c.1037+1G>A Pathogenic/Likely pathogenic ★★ same condition
OCLN p.Arg36Ter Pathogenic ★★ same condition
OCLN p.Thr158Ala Uncertain significance ★★ ⚠ same condition
OCLN p.Thr59Pro Uncertain significance ★★ ⚠ same condition
OCLN c.1037+5G>A Pathogenic ★ same condition
OCLN c.1254-1G>A Likely pathogenic ★ same condition
OCLN c.50+2T>C Likely pathogenic ★ same condition
OCLN p.Glu442Ter Pathogenic ★ 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-pro24ala (accessed [today's date]).

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