Is TYR p.Ala482= (c.1446G>C) pathogenic?

TYR p.Ala482= (c.1446G>C) is classified Conflicting classifications of pathogenicity in TYR (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-09-09). Ultra-rare (popmax 0.0165%, mid); Associated with oculocutaneous albinism type 1A.

What condition is associated with TYR p.Ala482= (c.1446G>C)?

TYR p.Ala482= (c.1446G>C) is associated with oculocutaneous albinism type 1A, oculocutaneous albinism (ClinVar).

How common is TYR p.Ala482= (c.1446G>C) in the general population?

TYR p.Ala482= (c.1446G>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

How is Oculocutaneous albinism type 1 inherited?

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

TYR p.Ala482=

c.1446G>C · rs3913543 · VCV499569

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

oculocutaneous albinism type 1A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.8	GERP -2.8
Overall
CADD	0.125	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,076 alleles

Filtering AF 0.00443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00403%

Overall 0.00459% 74/1,613,802 alleles · ultra-rare exomes 59/1,461,596 · genomes 15/152,206 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,076
Finnishnot grpmax-eligible	0.00781%	12,807
European (non-Finnish)	0.00551%	18,151
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
Remaining individualsnot grpmax-eligible	0.0032%	31,232

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: TYR
Protein: p.Ala482=
Coding: c.1446G>C
MANE Select: NM_000372
dbSNP: rs3913543
Type: single nucleotide variant
Location: chr11:89295222 (GRCh38)
Gene constraint: LOEUF 1.346 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.79 · 1 PDB

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

Disease context

oculocutaneous albinism type 1A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: oculocutaneous albinism

For Oculocutaneous albinism type 1 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

TYR p.Ala482Glu Likely pathogenic same residue
TYR p.Ala482Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
TYR p.Ala482Val Uncertain significance ★ ⚠ same residue
TYR c.1036+1G>A Pathogenic/Likely pathogenic ★★ same condition
TYR c.1036+2T>G Pathogenic ★★ same condition
TYR c.1037-1G>A Pathogenic/Likely pathogenic ★★ same condition
TYR c.1037-2A>G Pathogenic/Likely pathogenic ★★ same condition
TYR c.1037-3C>G 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/tyr-p-ala482 (accessed [today's date]).

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