Is RPS19 p.Pro89Arg (c.266C>G) pathogenic?

RPS19 p.Pro89Arg (c.266C>G) is classified Uncertain significance in RPS19 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-20). AlphaMissense: likely pathogenic (0.8179); Absent from gnomAD v4.1; Associated with Diamond-Blackfan anemia.

What condition is associated with RPS19 p.Pro89Arg (c.266C>G)?

RPS19 p.Pro89Arg (c.266C>G) is associated with Diamond-Blackfan anemia (ClinVar).

How common is RPS19 p.Pro89Arg (c.266C>G) in the general population?

RPS19 p.Pro89Arg (c.266C>G) is absent from gnomAD v4.1 (gnomAD).

How is Diamond-Blackfan anemia inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about RPS19 p.Pro89Arg (c.266C>G)?

AlphaMissense predicts likely pathogenic (score 0.8179) — an in-silico prediction, not a clinical call.

RPS19 p.Pro89Arg

c.266C>G · rs2513683154 · VCV2118121

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8179 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Diamond-Blackfan anemia

Computational evidence

Protein change
AlphaMissense	0.8179	likely pathogenic
REVEL	0.734	pathogenic-leaning
SaProt	LLR -15.21	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 11 kb · p 4e-09 · regional, not allelic
Overall
CADD	27.1	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: RPS19
Protein: p.Pro89Arg
Coding: c.266C>G
MANE Select: NM_001022
dbSNP: rs2513683154
Type: single nucleotide variant
Location: chr19:41869124 (GRCh38)
Gene constraint: LOEUF 0.239 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.01 · 205 PDB

Full RPS19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Diamond-Blackfan anemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Diamond-Blackfan anemia (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

RPS19 c.356+1G>A Likely pathogenic ★★ same condition
RPS19 c.412-2A>G Pathogenic/Likely pathogenic ★★ same condition
RPS19 p.Arg56Leu Likely pathogenic ★★ same condition
RPS19 p.Arg62Gln Pathogenic ★★ same condition
RPS19 p.Arg62Trp Pathogenic/Likely pathogenic ★★ same condition
RPS19 p.Arg94Ter Pathogenic ★★ same condition
RPS19 p.Gln105Ter Pathogenic/Likely pathogenic ★★ same condition
RPS19 p.Gln126Ter Pathogenic ★★ same condition

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/rps19-p-pro89arg (accessed [today's date]).

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