Is TYR p.Val377Glu (c.1130T>A) pathogenic?

TYR p.Val377Glu (c.1130T>A) is classified Conflicting classifications of pathogenicity in TYR (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-12-31). AlphaMissense: likely pathogenic (0.7076); Absent from gnomAD v4.1; Associated with oculocutaneous albinism type 1A.

What condition is associated with TYR p.Val377Glu (c.1130T>A)?

TYR p.Val377Glu (c.1130T>A) is associated with oculocutaneous albinism type 1A, oculocutaneous albinism type 1B (ClinVar).

How common is TYR p.Val377Glu (c.1130T>A) in the general population?

TYR p.Val377Glu (c.1130T>A) 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.Val377Glu (c.1130T>A)?

AlphaMissense predicts likely pathogenic (score 0.7076) — an in-silico prediction, not a clinical call.

TYR p.Val377Glu

c.1130T>A · rs2496618758 · VCV2704873

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7076 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oculocutaneous albinism type 1A

Computational evidence

Protein change
AlphaMissense	0.7076	likely pathogenic
REVEL	0.879	moderately pathogenic-leaning
SaProt	LLR -12.07	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 7.8	GERP 1.4, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 117 kb · p 0.00089 · regional, not allelic
Overall
CADD	27.0	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.Val377Glu
Coding: c.1130T>A
MANE Select: NM_000372
dbSNP: rs2496618758
Type: single nucleotide variant
Location: chr11:89227916 (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 type 1B

For Oculocutaneous albinism type 1 (Orphanet):

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

Similar variants

TYR p.Val377Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
TYR p.Val377Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
TYR p.Val377Leu Uncertain significance ★ ⚠ same residue
TYR p.Val377= 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
TYR c.1037-2A>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-val377glu (accessed [today's date]).

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