Is RPLP0 p.Ser148Phe (c.443C>T) pathogenic?

RPLP0 p.Ser148Phe (c.443C>T) is classified Uncertain significance in RPLP0 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-06). AlphaMissense: likely pathogenic (0.9685); Absent from gnomAD v4.1.

How common is RPLP0 p.Ser148Phe (c.443C>T) in the general population?

RPLP0 p.Ser148Phe (c.443C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RPLP0 p.Ser148Phe (c.443C>T)?

AlphaMissense predicts likely pathogenic (score 0.9685) — an in-silico prediction, not a clinical call.

RPLP0 p.Ser148Phe

c.443C>T · VCV4579415

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9685 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9685	likely pathogenic
REVEL	0.542	indeterminate
SaProt	LLR -11.26	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 9.8	GERP 2.4, phastCons 1
Regional constraint	o/e 0.31	constrained · MANE · 328 bp · p 3.6e-11 · regional, not allelic
Overall
CADD	31.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RPLP0
Protein: p.Ser148Phe
Coding: c.443C>T
MANE Select: NM_001002
Type: single nucleotide variant
Location: chr12:120198876 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.12 · 68 PDB
Residue 148: a β-strand

Full RPLP0 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RPLP0 p.Lys92= Benign ★★ same type
RPLP0 p.Ala288Asp Uncertain significance ★ ⚠ same type
RPLP0 p.Ala291Gly Uncertain significance ★ ⚠ same type
RPLP0 p.Ala292Val Uncertain significance ★ ⚠ same type
RPLP0 p.Arg214His Uncertain significance ★ ⚠ same type
RPLP0 p.Arg220Cys Uncertain significance ★ ⚠ same type
RPLP0 p.Arg220His Uncertain significance ★ ⚠ same type
RPLP0 p.Arg220Ser 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/rplp0-p-ser148phe (accessed [today's date]).

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