Is PRPF3 p.Ser320Phe (c.959C>T) pathogenic?

PRPF3 p.Ser320Phe (c.959C>T) is classified Uncertain significance in PRPF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-31). AlphaMissense: likely benign (0.2243); Very rare (popmax 0.005%, amr).

How common is PRPF3 p.Ser320Phe (c.959C>T) in the general population?

PRPF3 p.Ser320Phe (c.959C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about PRPF3 p.Ser320Phe (c.959C>T)?

AlphaMissense predicts likely benign (score 0.2243) — an in-silico prediction, not a clinical call.

PRPF3 p.Ser320Phe

c.959C>T · rs1553866975 · VCV2075590

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2243 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2243	likely benign
REVEL	0.47	indeterminate
SaProt	LLR -6.79	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 13 kb · p 7e-23 · regional, not allelic
Overall
CADD	28.2	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 0.005% Admixed American · 3/60,008 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000248% 4/1,614,104 alleles · very rare exomes 4/1,461,850 · genomes 0/152,254 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,003
European (non-Finnish)	8.47e-05%	1,179,994

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: PRPF3
Protein: p.Ser320Phe
Coding: c.959C>T
MANE Select: NM_004698
dbSNP: rs1553866975
Type: single nucleotide variant
Location: chr1:150335165 (GRCh38)
Gene constraint: LOEUF 0.087 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.75 · 30 PDB

Full PRPF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRPF3 p.Ser320Cys Uncertain significance ★ ⚠ same residue
PRPF3 p.Arg449Gly Pathogenic/Likely pathogenic ★★ same type
PRPF3 p.His499Pro Pathogenic ★★ same type
PRPF3 p.Pro493Ser Pathogenic ★★ same type
PRPF3 p.Thr494Met Pathogenic ★★ same type
PRPF3 p.Ala489Pro Uncertain significance ★★ ⚠ same type
PRPF3 p.Arg641Gln Uncertain significance ★★ ⚠ same type
PRPF3 p.Asp43Gly 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/prpf3-p-ser320phe (accessed [today's date]).

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