Is TYR p.Ser92Pro (c.274T>C) pathogenic?

TYR p.Ser92Pro (c.274T>C) is classified Likely pathogenic in TYR (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.255); Absent from gnomAD v4.1; Associated with oculocutaneous albinism type 1A.

What condition is associated with TYR p.Ser92Pro (c.274T>C)?

TYR p.Ser92Pro (c.274T>C) is associated with oculocutaneous albinism type 1A (ClinVar).

How common is TYR p.Ser92Pro (c.274T>C) in the general population?

TYR p.Ser92Pro (c.274T>C) is absent from gnomAD v4.1 (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.Ser92Pro (c.274T>C)?

AlphaMissense predicts likely benign (score 0.255) — an in-silico prediction, not a clinical call.

TYR p.Ser92Pro

c.274T>C · VCV3769584

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.255 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

oculocutaneous albinism type 1A

Computational evidence

Protein change
AlphaMissense	0.255	likely benign ⚠ discordant with ClinVar
REVEL	0.303	indeterminate
SaProt	LLR -8.13	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -0.98, phastCons 0.063
Regional constraint	o/e 1.13	unconstrained · MANE · 117 kb · p 0.00089 · regional, not allelic
Overall
CADD	18.63	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TYR
Protein: p.Ser92Pro
Coding: c.274T>C
MANE Select: NM_000372
Type: single nucleotide variant
Location: chr11:89178227 (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

For Oculocutaneous albinism type 1 (Orphanet):

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

Similar variants

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
TYR c.1366+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/tyr-p-ser92pro (accessed [today's date]).

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