Is PRPF4 p.Ser137Pro (c.409T>C) pathogenic?

PRPF4 p.Ser137Pro (c.409T>C) is classified Uncertain significance in PRPF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). AlphaMissense: likely pathogenic (0.9989); No allele count reported in gnomAD v4.1 (AN 1,604,126).

How common is PRPF4 p.Ser137Pro (c.409T>C) in the general population?

PRPF4 p.Ser137Pro (c.409T>C) is no allele count reported in gnomAD v4.1 (AN 1,604,126) (gnomAD).

What do computational predictors say about PRPF4 p.Ser137Pro (c.409T>C)?

AlphaMissense predicts likely pathogenic (score 0.9989) — an in-silico prediction, not a clinical call.

PRPF4 p.Ser137Pro

c.409T>C · rs2490807507 · VCV2809927

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9989 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,604,126)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9989	likely pathogenic · top 3% in PRPF4
REVEL	0.504	indeterminate
SaProt	LLR -14.71	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 16 kb · p 6e-12 · regional, not allelic
Overall
CADD	28.9	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S138P vs ClinVar S137P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,604,126). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PRPF4
Protein: p.Ser137Pro
Coding: c.409T>C
MANE Select: NM_001244926
dbSNP: rs2490807507
Type: single nucleotide variant
Location: chr9:113282662 (GRCh38)
Gene constraint: LOEUF 0.294 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.33 · 25 PDB

Full PRPF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRPF4 p.Ser137= Likely benign ★ same residue
PRPF4 p.Pro314Leu Likely pathogenic ★★ same type
PRPF4 c.654+4A>T Uncertain significance ★★ same type
PRPF4 p.Ala195Thr Uncertain significance ★★ ⚠ same type
PRPF4 p.Ala299Val Uncertain significance ★★ ⚠ same type
PRPF4 p.Arg206Ser Uncertain significance ★★ ⚠ same type
PRPF4 p.Arg438Trp Uncertain significance ★★ ⚠ same type
PRPF4 p.Arg439Cys Uncertain significance ★★ ⚠ 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/prpf4-p-ser137pro (accessed [today's date]).

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