Is PRPF3 p.Pro313Ser (c.937C>T) pathogenic?

PRPF3 p.Pro313Ser (c.937C>T) is classified Uncertain significance in PRPF3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-28). AlphaMissense: likely benign (0.0701); Very rare (popmax 0.00936%, afr).

How common is PRPF3 p.Pro313Ser (c.937C>T) in the general population?

PRPF3 p.Pro313Ser (c.937C>T) is very rare (popmax 0.00936%, afr) (gnomAD).

What do computational predictors say about PRPF3 p.Pro313Ser (c.937C>T)?

AlphaMissense predicts likely benign (score 0.0701) — an in-silico prediction, not a clinical call.

PRPF3 p.Pro313Ser

c.937C>T · rs1489549828 · VCV1005905

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0701 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00936%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0701	likely benign
REVEL	0.469	indeterminate
SaProt	LLR -10.50	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
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	22.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00936% African / African-American · 7/74,824 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000434% 7/1,613,674 alleles · very rare

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.Pro313Ser
Coding: c.937C>T
MANE Select: NM_004698
dbSNP: rs1489549828
Type: single nucleotide variant
Location: chr1:150335143 (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.Pro313Thr 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-pro313ser (accessed [today's date]).

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