Is OCA2 p.Val519fs (c.1555del) pathogenic?

OCA2 p.Val519fs (c.1555del) is classified Pathogenic/Likely pathogenic in OCA2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-02). Very rare (popmax 0.00267%, afr); Associated with OCA2-related disorder.

What condition is associated with OCA2 p.Val519fs (c.1555del)?

OCA2 p.Val519fs (c.1555del) is associated with OCA2-related disorder (ClinVar).

How common is OCA2 p.Val519fs (c.1555del) in the general population?

OCA2 p.Val519fs (c.1555del) is very rare (popmax 0.00267%, afr) (gnomAD).

OCA2 p.Val519fs

c.1555del · rs765235945 · VCV1458413

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

OCA2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 15 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,912 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,613,540 alleles · very rare exomes 1/1,461,368 · genomes 1/152,172 · joint denominator

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: OCA2
Protein: p.Val519fs
Coding: c.1555del
MANE Select: NM_000275
dbSNP: rs765235945
Type: Deletion
Location: chr15:27966771 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.79
Residue 519: a UniProt-annotated variant site (in)

Full OCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

OCA2-related disorder

Similar variants

OCA2 c.647-12_647-1del Likely pathogenic ★★ same condition
OCA2 p.Ala55fs Pathogenic/Likely pathogenic ★★ same condition
OCA2 p.Ala696fs Pathogenic/Likely pathogenic ★★ same condition
OCA2 p.Asn442del Likely pathogenic ★★ same condition
OCA2 p.Asn603fs Pathogenic/Likely pathogenic ★★ same condition
OCA2 p.Ile742fs Pathogenic/Likely pathogenic ★★ same condition
OCA2 p.Leu207_Leu212del Pathogenic/Likely pathogenic ★★ same condition
OCA2 p.Leu316_Leu317insTer Pathogenic/Likely 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/oca2-p-val519fs (accessed [today's date]).

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