Is TYR p.Pro384Ser (c.1150C>T) pathogenic?

TYR p.Pro384Ser (c.1150C>T) is classified Uncertain significance in TYR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-17). AlphaMissense: likely pathogenic (0.9108); Very rare (popmax 0.00133%, afr).

How common is TYR p.Pro384Ser (c.1150C>T) in the general population?

TYR p.Pro384Ser (c.1150C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about TYR p.Pro384Ser (c.1150C>T)?

AlphaMissense predicts likely pathogenic (score 0.9108) — an in-silico prediction, not a clinical call.

TYR p.Pro384Ser

c.1150C>T · VCV3339476

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9108 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9108	likely pathogenic
REVEL	0.981	strongly pathogenic-leaning
SaProt	LLR -14.07	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 5.9	GERP 1.4, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 117 kb · p 0.00089 · regional, not allelic
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,958 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,613,468 alleles · very rare exomes 5/1,461,346 · genomes 0/152,122 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,958
European (non-Finnish)	0.000339%	294,918

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.Pro384Ser
Coding: c.1150C>T
MANE Select: NM_000372
Type: single nucleotide variant
Location: chr11:89227936 (GRCh38)
Gene constraint: LOEUF 1.346 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.79 · 1 PDB
Residue 384: a UniProt-annotated variant site (in oca1a)

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

Similar variants

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
TYR c.1185-2A>G Pathogenic/Likely pathogenic ★★ same type
TYR c.1366+1G>T 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-pro384ser (accessed [today's date]).

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