Is TYR p.Arg217Pro (c.650G>C) pathogenic?

TYR p.Arg217Pro (c.650G>C) is classified Likely pathogenic in TYR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-05). AlphaMissense: likely pathogenic (0.768); Very rare (popmax 8.48e-05%, nfe); Associated with oculocutaneous albinism type 1A.

What condition is associated with TYR p.Arg217Pro (c.650G>C)?

TYR p.Arg217Pro (c.650G>C) is associated with oculocutaneous albinism type 1A, oculocutaneous albinism type 1B (ClinVar).

How common is TYR p.Arg217Pro (c.650G>C) in the general population?

TYR p.Arg217Pro (c.650G>C) is very rare (popmax 8.48e-05%, nfe) (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.Arg217Pro (c.650G>C)?

AlphaMissense predicts likely pathogenic (score 0.768) — an in-silico prediction, not a clinical call.

TYR p.Arg217Pro

c.650G>C · VCV3574114

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.768 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oculocutaneous albinism type 1A

Computational evidence

Protein change
AlphaMissense	0.768	likely pathogenic ✓ concordant with ClinVar
REVEL	0.686	pathogenic-leaning
SaProt	LLR -12.92	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 0.98	GERP -0.58, phastCons 0.47
Regional constraint	o/e 1.13	unconstrained · MANE · 117 kb · p 0.00089 · regional, not allelic
Overall
CADD	17.25	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 8.48e-05% European (non-Finnish) · 1/1,179,202 alleles

Overall 6.2e-05% 1/1,612,568 alleles · very rare exomes 0/1,460,492 · genomes 1/152,076 · 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: TYR
Protein: p.Arg217Pro
Coding: c.650G>C
MANE Select: NM_000372
Type: single nucleotide variant
Location: chr11:89178603 (GRCh38)
Gene constraint: LOEUF 1.346 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.79 · 1 PDB
Residue 217: 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.Arg217Gln Pathogenic/Likely pathogenic ★★ ⚠ same residue
TYR p.Arg217Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
TYR p.Arg217fs Pathogenic ★★ same residue
TYR p.Arg217Gly Pathogenic ★ ⚠ same residue
TYR p.Arg217= Likely benign ★ 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

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-arg217pro (accessed [today's date]).

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