Is PRPF3 p.Ser4= (c.12A>G) pathogenic?

PRPF3 p.Ser4= (c.12A>G) is classified Likely benign in PRPF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-13). Very rare (popmax 0.0011%, sas).

How common is PRPF3 p.Ser4= (c.12A>G) in the general population?

PRPF3 p.Ser4= (c.12A>G) is very rare (popmax 0.0011%, sas) (gnomAD).

PRPF3 p.Ser4=

c.12A>G · VCV4909425

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -3.2, phastCons 0.001
Overall
CADD	3.943	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,018 alleles

Overall 6.85e-05% 1/1,460,464 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.Ser4=
Coding: c.12A>G
MANE Select: NM_004698
Type: single nucleotide variant
Location: chr1:150324954 (GRCh38)
Gene constraint: LOEUF 0.087 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.75 · 30 PDB
Residue 4: the pwi domain

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

Similar variants

PRPF3 p.Ser4Leu 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-ser4 (accessed [today's date]).

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