Is OCA2 p.Ala16= (c.48G>A) pathogenic?

OCA2 p.Ala16= (c.48G>A) is classified Conflicting classifications of pathogenicity in OCA2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-05-29). Rare (popmax 0.276%, eas); Associated with oculocutaneous albinism type 2.

What condition is associated with OCA2 p.Ala16= (c.48G>A)?

OCA2 p.Ala16= (c.48G>A) is associated with oculocutaneous albinism type 2 (ClinVar).

How common is OCA2 p.Ala16= (c.48G>A) in the general population?

OCA2 p.Ala16= (c.48G>A) is rare (popmax 0.276%, eas) (gnomAD).

How is Oculocutaneous albinism type 2 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

OCA2 p.Ala16=

c.48G>A · rs371834997 · VCV315478

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.276%, eas)

Conditions

oculocutaneous albinism type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.23	phastCons 0.23
Overall
CADD	4.006	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.276% East Asian · 124/44,858 alleles

Filtering AF 0.237% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.222%

Overall 0.0116% 187/1,611,764 alleles · rare exomes 163/1,459,424 · genomes 24/152,340 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.276%	362
African / African-American	0.0213%	4,692
Finnishnot grpmax-eligible	0.0193%	5,179
European (non-Finnish)	0.00271%	36,867
Admixed American	0.00167%	59,994
Remaining individualsnot grpmax-eligible	0.0016%	62,384
South Asian	0.0011%	91,030

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.Ala16=
Coding: c.48G>A
MANE Select: NM_000275
dbSNP: rs371834997
Type: single nucleotide variant
Location: chr15:28081827 (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 type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Oculocutaneous albinism type 2 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 6-9 / 10 000 (Specific population)

Similar variants

OCA2 p.Ala16Thr Uncertain significance ★ ⚠ same residue
OCA2 c.1044+1G>T Pathogenic ★★ same condition
OCA2 c.1045-15T>G Pathogenic/Likely pathogenic ★★ same condition
OCA2 c.1182+1G>A Pathogenic ★★ same condition
OCA2 c.1365-1G>A Pathogenic ★★ same condition
OCA2 c.1503+5G>A Pathogenic/Likely pathogenic ★★ same condition
OCA2 c.1504-2A>G Pathogenic/Likely pathogenic ★★ same condition
OCA2 c.1842+1G>T 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-ala16 (accessed [today's date]).

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