Is PRPF19 p.Pro151Ser (c.451C>T) pathogenic?

PRPF19 p.Pro151Ser (c.451C>T) is classified Uncertain significance in PRPF19 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-20). AlphaMissense: likely benign (0.0666); Very rare (popmax 0.000763%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PRPF19 p.Pro151Ser (c.451C>T)?

PRPF19 p.Pro151Ser (c.451C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PRPF19 p.Pro151Ser (c.451C>T) in the general population?

PRPF19 p.Pro151Ser (c.451C>T) is very rare (popmax 0.000763%, nfe) (gnomAD).

What do computational predictors say about PRPF19 p.Pro151Ser (c.451C>T)?

AlphaMissense predicts likely benign (score 0.0666) — an in-silico prediction, not a clinical call.

PRPF19 p.Pro151Ser

c.451C>T · VCV4862553

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0666 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0666	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -6.63	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 4,434 bp · p 1.2e-19 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.000763% European (non-Finnish) · 9/1,179,724 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000558% 9/1,613,860 alleles · very rare exomes 9/1,461,524 · genomes 0/152,336 · 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: PRPF19
Protein: p.Pro151Ser
Coding: c.451C>T
MANE Select: NM_014502
Type: single nucleotide variant
Location: chr11:60902594 (GRCh38)
Gene constraint: LOEUF 0.099 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.35 · 27 PDB
Residue 151: the 'may mediate interaction with psmc5' region

Full PRPF19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRPF19 p.Ile172Ser Likely pathogenic ★ same condition
PRPF19 p.Ala35Val Uncertain significance ★ ⚠ same condition
PRPF19 p.Ala487Thr Uncertain significance ★ ⚠ same condition
PRPF19 p.Ala491Thr Uncertain significance ★ ⚠ same condition
PRPF19 p.Arg100Gly Uncertain significance ★ ⚠ same condition
PRPF19 p.Arg303Gln Uncertain significance ★ ⚠ same condition
PRPF19 p.Asn434Asp Uncertain significance ★ ⚠ same condition
PRPF19 p.Asn434Ile Uncertain significance ★ ⚠ 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/prpf19-p-pro151ser (accessed [today's date]).

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