Is RPS19 p.Pro2= (c.6T>G) pathogenic?

RPS19 p.Pro2= (c.6T>G) is classified Likely benign in RPS19 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-17). Very rare (popmax 0.00432%, nfe); Associated with Diamond-Blackfan anemia.

What condition is associated with RPS19 p.Pro2= (c.6T>G)?

RPS19 p.Pro2= (c.6T>G) is associated with Diamond-Blackfan anemia (ClinVar).

How common is RPS19 p.Pro2= (c.6T>G) in the general population?

RPS19 p.Pro2= (c.6T>G) is very rare (popmax 0.00432%, nfe) (gnomAD).

How is Diamond-Blackfan anemia inherited?

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

RPS19 p.Pro2=

c.6T>G · rs782512026 · VCV1563472

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00432%, nfe)

Conditions

Diamond-Blackfan anemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.84	GERP -3.7, phastCons 0.012
Overall
CADD	11.56	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00432% European (non-Finnish) · 51/1,179,346 alleles

Filtering AF 0.00334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00302%

Overall 0.00363% 53/1,461,092 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00432%	23,124
Remaining individualsnot grpmax-eligible	0.0032%	31,239

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: RPS19
Protein: p.Pro2=
Coding: c.6T>G
MANE Select: NM_001022
dbSNP: rs782512026
Type: single nucleotide variant
Location: chr19:41860780 (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 p.Pro2Leu Uncertain significance ★ ⚠ same residue
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

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-pro2 (accessed [today's date]).

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