Is MRPS34 p.Arg27Lys (c.80G>A) pathogenic?

MRPS34 p.Arg27Lys (c.80G>A) is classified Uncertain significance in MRPS34 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-11). AlphaMissense: likely benign (0.1433); Ultra-rare (popmax 0.0872%, sas); Associated with Inborn genetic diseases.

What condition is associated with MRPS34 p.Arg27Lys (c.80G>A)?

MRPS34 p.Arg27Lys (c.80G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MRPS34 p.Arg27Lys (c.80G>A) in the general population?

MRPS34 p.Arg27Lys (c.80G>A) is ultra-rare (popmax 0.0872%, sas) (gnomAD).

What do computational predictors say about MRPS34 p.Arg27Lys (c.80G>A)?

AlphaMissense predicts likely benign (score 0.1433) — an in-silico prediction, not a clinical call.

MRPS34 p.Arg27Lys

c.80G>A · rs759517804 · VCV2074687

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1433 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0872%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1433	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -6.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.2	GERP -0.58, phastCons 0.59
Regional constraint	o/e 1.25	unconstrained · MANE · 895 bp · p 4.8e-06 · regional, not allelic
Overall
CADD	16.34	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0872% South Asian · 59/67,698 alleles

Filtering AF 0.0693% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0629%

Overall 0.0046% 66/1,435,470 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0872%	1,147
African / African-American	0.003%	33,288
Admixed American	0.00299%	33,464
European (non-Finnish)	0.000365%	274,048

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.Arg27Lys
Coding: c.80G>A
MANE Select: NM_001257370 · reported on NM_023936
dbSNP: rs759517804
Type: single nucleotide variant
Location: chr16:1773040 (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-arg27lys (accessed [today's date]).

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