Is MRPS34 p.Arg9Gln (c.26G>A) pathogenic?

MRPS34 p.Arg9Gln (c.26G>A) is classified Uncertain significance in MRPS34 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-24). AlphaMissense: ambiguous (0.5028); Ultra-rare (popmax 0.0455%, afr); Associated with Inborn genetic diseases.

What condition is associated with MRPS34 p.Arg9Gln (c.26G>A)?

MRPS34 p.Arg9Gln (c.26G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MRPS34 p.Arg9Gln (c.26G>A) in the general population?

MRPS34 p.Arg9Gln (c.26G>A) is ultra-rare (popmax 0.0455%, afr) (gnomAD).

What do computational predictors say about MRPS34 p.Arg9Gln (c.26G>A)?

AlphaMissense predicts ambiguous (score 0.5028) — an in-silico prediction, not a clinical call.

MRPS34 p.Arg9Gln

c.26G>A · rs534007365 · VCV2383100

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.5028 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0455%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5028	ambiguous
REVEL	0.261	benign-leaning
SaProt	LLR -5.90	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.2	GERP 1.7, phastCons 1
Regional constraint	o/e 1.25	unconstrained · MANE · 895 bp · p 4.8e-06 · regional, not allelic
Overall
CADD	29.1	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

Grpmax group 0.0455% African / African-American · 30/65,972 alleles

Filtering AF 0.0326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0284%

Overall 0.00328% 46/1,404,388 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0455%	2,199
South Asian	0.0159%	6,292
Admixed American	0.00335%	29,876
Remaining individualsnot grpmax-eligible	0.00186%	53,742
European (non-Finnish)	0.000369%	271,025

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: MRPS34
Protein: p.Arg9Gln
Coding: c.26G>A
MANE Select: NM_001257370 · reported on NM_023936
dbSNP: rs534007365
Type: single nucleotide variant
Location: chr16:1773094 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-arg9gln (accessed [today's date]).

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