Is RPS26 p.Asp33= (c.99C>T) pathogenic?

RPS26 p.Asp33= (c.99C>T) is classified Likely benign in RPS26 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-30). Very rare (popmax 0.00167%, amr); Associated with Diamond-Blackfan anemia.

What condition is associated with RPS26 p.Asp33= (c.99C>T)?

RPS26 p.Asp33= (c.99C>T) is associated with Diamond-Blackfan anemia (ClinVar).

How common is RPS26 p.Asp33= (c.99C>T) in the general population?

RPS26 p.Asp33= (c.99C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Diamond-Blackfan anemia inherited?

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

RPS26 p.Asp33=

c.99C>T · rs753296520 · VCV3232372

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 -0.75	GERP -4, phastCons 0.009
Overall
CADD	8.029	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,018 alleles

Overall 0.000187% 3/1,602,690 alleles · very rare exomes 3/1,450,350 · genomes 0/152,340 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,018
Remaining individualsnot grpmax-eligible	0.0016%	62,362
European (non-Finnish)	8.5e-05%	1,177,011

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: RPS26
Protein: p.Asp33=
Coding: c.99C>T
MANE Select: NM_001029
dbSNP: rs753296520
Type: single nucleotide variant
Location: chr12:56042520 (GRCh38)
Gene constraint: LOEUF 0.32 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 86.09 · 185 PDB
Residue 33: a turn; a UniProt-annotated variant site (in dba10)

Full RPS26 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

RPS26 p.Asp33Val Uncertain significance ★ ⚠ same residue
RPS26 p.Asp33Asn Pathogenic same residue
RPS26 c.3+1G>T Pathogenic/Likely pathogenic ★★ same condition
RPS26 p.Arg87Ter Pathogenic ★★ same condition
RPS26 p.Gln19Ter Pathogenic/Likely pathogenic ★★ same condition
RPS26 p.Met1Thr Pathogenic ★★ same condition
RPS26 p.Met1Val Pathogenic ★★ same condition
RPS26 p.Glu90= Likely benign ★★ 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/rps26-p-asp33 (accessed [today's date]).

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