Is RPS26 p.Pro99= (c.297C>T) pathogenic?

RPS26 p.Pro99= (c.297C>T) is classified Uncertain significance in RPS26 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). Very rare (popmax 0.00167%, amr); Associated with Diamond-Blackfan anemia 10.

What condition is associated with RPS26 p.Pro99= (c.297C>T)?

RPS26 p.Pro99= (c.297C>T) is associated with Diamond-Blackfan anemia 10 (ClinVar).

How common is RPS26 p.Pro99= (c.297C>T) in the general population?

RPS26 p.Pro99= (c.297C>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.Pro99=

c.297C>T · VCV3574994

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Diamond-Blackfan anemia 10

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 -0.82	GERP -1.3
Overall
CADD	8.846	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,976 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,613,662 alleles · very rare exomes 5/1,461,590 · genomes 1/152,072 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,976
European (non-Finnish)	0.000424%	235,980

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.Pro99=
Coding: c.297C>T
MANE Select: NM_001029
Type: single nucleotide variant
Location: chr12:56043478 (GRCh38)
Gene constraint: LOEUF 0.32 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 86.09 · 185 PDB
Residue 99: the 'disordered' region; an α-helix

Full RPS26 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Diamond-Blackfan anemia 10 — 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.Pro99Ser Uncertain significance ⚠ same residue
RPS26 c.3+1G>T Pathogenic/Likely pathogenic ★★ same condition
RPS26 c.3+2T>G Likely pathogenic ★★ same condition
RPS26 p.Arg28Ter 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

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-pro99 (accessed [today's date]).

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