Is TYR p.Arg299Ser (c.895C>A) pathogenic?

TYR p.Arg299Ser (c.895C>A) is classified Pathogenic/Likely pathogenic in TYR (ClinVar, Multiple submitters, 10 submitters; last evaluated 2024-10-10). AlphaMissense: likely pathogenic (0.9946); Ultra-rare (popmax 0.0111%, eas); Associated with oculocutaneous albinism type 1A.

What condition is associated with TYR p.Arg299Ser (c.895C>A)?

TYR p.Arg299Ser (c.895C>A) is associated with oculocutaneous albinism type 1A, oculocutaneous albinism type 1B (ClinVar).

How common is TYR p.Arg299Ser (c.895C>A) in the general population?

TYR p.Arg299Ser (c.895C>A) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

How is Oculocutaneous albinism type 1 inherited?

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

What do computational predictors say about TYR p.Arg299Ser (c.895C>A)?

AlphaMissense predicts likely pathogenic (score 0.9946) — an in-silico prediction, not a clinical call.

TYR p.Arg299Ser

c.895C>A · rs61754374 · VCV99587

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely pathogenic

0.9946 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oculocutaneous albinism type 1A

Computational evidence

Protein change
AlphaMissense	0.9946	likely pathogenic ✓ concordant with ClinVar · top 1% in TYR
REVEL	0.886	moderately pathogenic-leaning
SaProt	LLR -15.46	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.78, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 117 kb · p 0.00089 · regional, not allelic
Overall
CADD	23.2	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 0.0111% East Asian · 5/44,858 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.000434% 7/1,613,474 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,972
African / African-American	0.00134%	74,838
European (non-Finnish)	8.48e-05%	1,179,770

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.Arg299Ser
Coding: c.895C>A
MANE Select: NM_000372
dbSNP: rs61754374
Type: single nucleotide variant
Location: chr11:89191277 (GRCh38)
Gene constraint: LOEUF 1.346 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.79 · 1 PDB
Residue 299: the 'disordered' region; a UniProt-annotated variant site (in oca1a)

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 type 1B

For Oculocutaneous albinism type 1 (Orphanet):

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

Similar variants

TYR p.Arg299His Pathogenic ★★ same residue
TYR p.Arg299Cys Conflicting classifications of pathogenicity ★ ⚠ 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
TYR c.1037-7T>A 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-arg299ser (accessed [today's date]).

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