Is PRP4K p.Arg464Ser (c.1392A>C) pathogenic?

PRP4K p.Arg464Ser (c.1392A>C) is classified Uncertain significance in PRP4K (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-21). AlphaMissense: likely pathogenic (0.8036); Ultra-rare (popmax 0.0342%, nfe).

How common is PRP4K p.Arg464Ser (c.1392A>C) in the general population?

PRP4K p.Arg464Ser (c.1392A>C) is ultra-rare (popmax 0.0342%, nfe) (gnomAD).

What do computational predictors say about PRP4K p.Arg464Ser (c.1392A>C)?

AlphaMissense predicts likely pathogenic (score 0.8036) — an in-silico prediction, not a clinical call.

PRP4K p.Arg464Ser

c.1392A>C · rs34976464 · VCV2377184

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8036 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0342%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8036	likely pathogenic
REVEL	0.376	indeterminate
SaProt	LLR -10.30	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.4	GERP 0.67, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 11 kb · p 0.61 · regional, not allelic
Overall
CADD	19.23	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0342% European (non-Finnish) · 404/1,179,810 alleles

Filtering AF 0.0315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0304%

Overall 0.0269% 434/1,613,494 alleles · ultra-rare exomes 428/1,461,370 · genomes 6/152,124 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0342%	2,920
South Asian	0.0275%	3,640
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,590
Remaining individualsnot grpmax-eligible	0.0032%	31,237
Admixed American	0.00167%	59,898
African / African-American	0.00134%	74,852

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: PRP4K
Protein: p.Arg464Ser
Coding: c.1392A>C
MANE Select: NM_003913
dbSNP: rs34976464
Type: single nucleotide variant
Location: chr6:4037550 (GRCh38)
Structure: AlphaFold pLDDT 60.24 · 14 PDB
Residue 464: the 'disordered' region

Full PRP4K gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRP4K p.Arg464= Likely benign ★ same residue
PRP4K p.Ala671Thr Uncertain significance ★ same type
PRP4K p.Arg10Trp Uncertain significance ★ ⚠ same type
PRP4K p.Arg183Gln Uncertain significance ★ ⚠ same type
PRP4K p.Arg191Trp Uncertain significance ★ ⚠ same type
PRP4K p.Arg308Gln Uncertain significance ★ ⚠ same type
PRP4K p.Arg308Gly Uncertain significance ★ ⚠ same type
PRP4K p.Arg344Gly 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/prp4k-p-arg464ser (accessed [today's date]).

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