Is MRPS9 p.Arg145Pro (c.434G>C) pathogenic?

MRPS9 p.Arg145Pro (c.434G>C) is classified Uncertain significance in MRPS9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). AlphaMissense: likely pathogenic (0.9839); Absent from gnomAD v4.1.

How common is MRPS9 p.Arg145Pro (c.434G>C) in the general population?

MRPS9 p.Arg145Pro (c.434G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MRPS9 p.Arg145Pro (c.434G>C)?

AlphaMissense predicts likely pathogenic (score 0.9839) — an in-silico prediction, not a clinical call.

MRPS9 p.Arg145Pro

c.434G>C · VCV3398406

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9839 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9839	likely pathogenic · top 1% in MRPS9
REVEL	0.844	moderately pathogenic-leaning
SaProt	LLR -17.97	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.21	acceptor loss, 24 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 9.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 62 kb · p 0.71 · regional, not allelic
Overall
CADD	29.3	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: MRPS9
Protein: p.Arg145Pro
Coding: c.434G>C
MANE Select: NM_182640
Type: single nucleotide variant
Location: chr2:105080007 (GRCh38)
Gene constraint: LOEUF 1.26 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.49 · 86 PDB

Full MRPS9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MRPS9 p.Ala11Val Uncertain significance ★ ⚠ same type
MRPS9 p.Ala236Ser Uncertain significance ★ ⚠ same type
MRPS9 p.Ala281Val Uncertain significance ★ ⚠ same type
MRPS9 p.Ala339Thr Uncertain significance ★ ⚠ same type
MRPS9 p.Arg243Ser Uncertain significance ★ ⚠ same type
MRPS9 p.Arg276Gly Uncertain significance ★ ⚠ same type
MRPS9 p.Arg375Cys Uncertain significance ★ ⚠ same type
MRPS9 p.Asn82Ser 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/mrps9-p-arg145pro (accessed [today's date]).

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