Is PRPF4 p.Ser287Phe (c.860C>T) pathogenic?

PRPF4 p.Ser287Phe (c.860C>T) is classified Uncertain significance in PRPF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-15). AlphaMissense: likely benign (0.1485); Very rare (popmax 0.00178%, nfe).

How common is PRPF4 p.Ser287Phe (c.860C>T) in the general population?

PRPF4 p.Ser287Phe (c.860C>T) is very rare (popmax 0.00178%, nfe) (gnomAD).

What do computational predictors say about PRPF4 p.Ser287Phe (c.860C>T)?

AlphaMissense predicts likely benign (score 0.1485) — an in-silico prediction, not a clinical call.

PRPF4 p.Ser287Phe

c.860C>T · VCV4904122

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1485 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1485	likely benign
REVEL	0.316	indeterminate
SaProt	LLR -6.77	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 16 kb · p 6e-12 · regional, not allelic
Overall
CADD	24.9	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S288F vs ClinVar S287F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00178% European (non-Finnish) · 21/1,180,024 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00143% 23/1,614,028 alleles · very rare exomes 22/1,461,876 · genomes 1/152,152 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00178%	56,192
Finnishnot grpmax-eligible	0.00156%	64,020
South Asian	0.0011%	91,084

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: PRPF4
Protein: p.Ser287Phe
Coding: c.860C>T
MANE Select: NM_001244926
Type: single nucleotide variant
Location: chr9:113286756 (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.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
PRPF4 p.Asn241Ser 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-ser287phe (accessed [today's date]).

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