Is OCA2 p.Phe685fs (c.2055del) pathogenic?

OCA2 p.Phe685fs (c.2055del) is classified Pathogenic in OCA2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-05-07). Very rare (popmax 0.00661%, nfe); Associated with oculocutaneous albinism.

What condition is associated with OCA2 p.Phe685fs (c.2055del)?

OCA2 p.Phe685fs (c.2055del) is associated with oculocutaneous albinism, oculocutaneous albinism type 2 (ClinVar).

How common is OCA2 p.Phe685fs (c.2055del) in the general population?

OCA2 p.Phe685fs (c.2055del) is very rare (popmax 0.00661%, nfe) (gnomAD).

OCA2 p.Phe685fs

c.2055del · rs772595552 · VCV430966

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00661%, nfe)

Conditions

oculocutaneous albinism

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 19 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	phastCons 1
Overall
CADD	26.4	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 0.00661% European (non-Finnish) · 78/1,179,958 alleles

Filtering AF 0.00538% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00498%

Overall 0.0049% 79/1,613,864 alleles · very rare exomes 76/1,461,792 · genomes 3/152,072 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00661%	15,128
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Phe685fs
Coding: c.2055del
MANE Select: NM_000275
dbSNP: rs772595552
Type: Deletion
Location: chr15:27926151 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.79

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

Disease context

oculocutaneous albinism — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: oculocutaneous albinism type 2

Similar variants

OCA2 p.Ala696fs Pathogenic/Likely pathogenic ★★ same condition
OCA2 p.Arg137fs Pathogenic ★★ same condition
OCA2 p.Arg53fs Pathogenic/Likely pathogenic ★★ same condition
OCA2 p.Asn603fs Pathogenic/Likely pathogenic ★★ same condition
OCA2 p.Glu253fs Pathogenic ★★ same condition
OCA2 p.Gly44fs Pathogenic/Likely pathogenic ★★ same condition
OCA2 p.Leu189fs Pathogenic ★★ same condition
OCA2 p.Leu207_Leu212del 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-phe685fs (accessed [today's date]).

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