Is OCLN p.Val157Phe (c.469G>T) pathogenic?

OCLN p.Val157Phe (c.469G>T) is classified Conflicting classifications of pathogenicity in OCLN (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-11). AlphaMissense: likely benign (0.2423); Rare (popmax 0.34%, afr).

How common is OCLN p.Val157Phe (c.469G>T) in the general population?

OCLN p.Val157Phe (c.469G>T) is rare (popmax 0.34%, afr) (gnomAD).

What do computational predictors say about OCLN p.Val157Phe (c.469G>T)?

AlphaMissense predicts likely benign (score 0.2423) — an in-silico prediction, not a clinical call.

OCLN p.Val157Phe

c.469G>T · rs139928771 · VCV546084

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2423 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.34%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2423	likely benign
REVEL	0.237	benign-leaning
SaProt	LLR -4.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.2	phastCons 0.99
Regional constraint	o/e 0.85	unconstrained · MANE · 9,860 bp · p 0.0048 · regional, not allelic
Overall
CADD	21.3	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 0.34% African / African-American · 255/74,928 alleles

Filtering AF 0.306% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.293%

Overall 0.0173% 279/1,614,034 alleles · rare exomes 138/1,461,888 · genomes 141/152,146 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.34%	294
Remaining individualsnot grpmax-eligible	0.0208%	4,807
Admixed American	0.0183%	5,454

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.Val157Phe
Coding: c.469G>T
MANE Select: NM_001205254
dbSNP: rs139928771
Type: single nucleotide variant
Location: chr5:69509559 (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 157: the marvel domain

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

Similar variants

OCLN p.Val157Ile 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-val157phe (accessed [today's date]).

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