Is MRPS34 p.Arg129Pro (c.386G>C) pathogenic?

MRPS34 p.Arg129Pro (c.386G>C) is classified Uncertain significance in MRPS34 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-11). AlphaMissense: likely pathogenic (0.7729); Absent from gnomAD v4.1.

How common is MRPS34 p.Arg129Pro (c.386G>C) in the general population?

MRPS34 p.Arg129Pro (c.386G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MRPS34 p.Arg129Pro (c.386G>C)?

AlphaMissense predicts likely pathogenic (score 0.7729) — an in-silico prediction, not a clinical call.

MRPS34 p.Arg129Pro

c.386G>C · rs1269280274 · VCV2130804

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7729 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7729	likely pathogenic · top 9% in MRPS34
REVEL	0.154	moderately benign-leaning
SaProt	LLR -14.91	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.25	unconstrained · MANE · 895 bp · p 4.8e-06 · regional, not allelic
Overall
CADD	27.5	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

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: MRPS34
Protein: p.Arg129Pro
Coding: c.386G>C
MANE Select: NM_023936
dbSNP: rs1269280274
Type: single nucleotide variant
Location: chr16:1772492 (GRCh38)
Gene constraint: LOEUF 1.89 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.20 · 85 PDB
Residue 129: a β-strand; a UniProt-annotated variant site (in coxpd32; significant decrease in protein levels; destabilizes the small ribosomal subunit resulting in impaired mitochondrial translation)

Full MRPS34 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MRPS34 c.322-10G>A Pathogenic ★★ same type
MRPS34 p.Glu23Lys Uncertain significance ★★ ⚠ same type
MRPS34 p.Ile196Lys Uncertain significance ★★ ⚠ same type
MRPS34 p.Lys144Asn Uncertain significance ★★ ⚠ same type
MRPS34 p.Met135Thr Uncertain significance ★★ same type
MRPS34 c.322-19C>T Likely benign ★★ same type
MRPS34 c.364+9C>T Benign/Likely benign ★★ same type
MRPS34 c.*63A>G Benign ★★ 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/mrps34-p-arg129pro (accessed [today's date]).

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