Is TYR p.Pro152Arg (c.455C>G) pathogenic?

TYR p.Pro152Arg (c.455C>G) is classified Uncertain significance in TYR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-04). AlphaMissense: likely pathogenic (0.6616); Absent from gnomAD v4.1.

How common is TYR p.Pro152Arg (c.455C>G) in the general population?

TYR p.Pro152Arg (c.455C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TYR p.Pro152Arg (c.455C>G)?

AlphaMissense predicts likely pathogenic (score 0.6616) — an in-silico prediction, not a clinical call.

TYR p.Pro152Arg

c.455C>G · rs1464062644 · VCV2130645

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6616 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6616	likely pathogenic
REVEL	0.423	indeterminate
SaProt	LLR -3.91	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 117 kb · p 0.00089 · regional, not allelic
Overall
CADD	23.5	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.Pro152Arg
Coding: c.455C>G
MANE Select: NM_000372
dbSNP: rs1464062644
Type: single nucleotide variant
Location: chr11:89178408 (GRCh38)
Gene constraint: LOEUF 1.346 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.79 · 1 PDB
Residue 152: a UniProt-annotated variant site (in oca1b)

Full TYR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TYR p.Pro152His Pathogenic ★ ⚠ same residue
TYR p.Pro152Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
TYR c.1036+1G>A Pathogenic/Likely pathogenic ★★ same type
TYR c.1036+2T>G Pathogenic ★★ same type
TYR c.1037-1G>A Pathogenic/Likely pathogenic ★★ same type
TYR c.1037-2A>G Pathogenic/Likely pathogenic ★★ same type
TYR c.1037-3C>G Pathogenic/Likely pathogenic ★★ same type
TYR c.1037-7T>A Pathogenic/Likely pathogenic ★★ same type

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-pro152arg (accessed [today's date]).

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