Is TYR p.Ser44Arg (c.132T>A) pathogenic?

TYR p.Ser44Arg (c.132T>A) is classified Pathogenic in TYR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-08). AlphaMissense: likely pathogenic (0.8521); Very rare (popmax 0.00833%, amr); Associated with oculocutaneous albinism type 1A.

What condition is associated with TYR p.Ser44Arg (c.132T>A)?

TYR p.Ser44Arg (c.132T>A) is associated with oculocutaneous albinism type 1A (ClinVar).

How common is TYR p.Ser44Arg (c.132T>A) in the general population?

TYR p.Ser44Arg (c.132T>A) is very rare (popmax 0.00833%, amr) (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.Ser44Arg (c.132T>A)?

AlphaMissense predicts likely pathogenic (score 0.8521) — an in-silico prediction, not a clinical call.

TYR p.Ser44Arg

c.132T>A · rs755700581 · VCV1066111

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8521 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oculocutaneous albinism type 1A

Computational evidence

Protein change
AlphaMissense	0.8521	likely pathogenic ✓ concordant with ClinVar
REVEL	0.84	moderately pathogenic-leaning
SaProt	LLR -7.53	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.12	GERP -2.9, phastCons 0.98
Regional constraint	o/e 1.13	unconstrained · MANE · 117 kb · p 0.00089 · regional, not allelic
Overall
CADD	20.8	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 0.00833% Admixed American · 5/60,008 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00031% 5/1,614,060 alleles · very rare exomes 5/1,461,886 · genomes 0/152,174 · 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.Ser44Arg
Coding: c.132T>A
MANE Select: NM_000372
dbSNP: rs755700581
Type: single nucleotide variant
Location: chr11:89178085 (GRCh38)
Gene constraint: LOEUF 1.346 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.79 · 1 PDB
Residue 44: 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

For Oculocutaneous albinism type 1 (Orphanet):

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

Similar variants

TYR p.Ser44Asn Likely pathogenic ★ ⚠ 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
TYR c.1185-2A>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-ser44arg (accessed [today's date]).

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