Is RPS26 p.Pro103Ser (c.307C>T) pathogenic?

RPS26 p.Pro103Ser (c.307C>T) is classified Uncertain significance in RPS26 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-17). AlphaMissense: likely benign (0.3097); Very rare (popmax 8.48e-05%, nfe); Associated with Diamond-Blackfan anemia 10.

What condition is associated with RPS26 p.Pro103Ser (c.307C>T)?

RPS26 p.Pro103Ser (c.307C>T) is associated with Diamond-Blackfan anemia 10 (ClinVar).

How common is RPS26 p.Pro103Ser (c.307C>T) in the general population?

RPS26 p.Pro103Ser (c.307C>T) is very rare (popmax 8.48e-05%, nfe) (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 RPS26 p.Pro103Ser (c.307C>T)?

AlphaMissense predicts likely benign (score 0.3097) — an in-silico prediction, not a clinical call.

RPS26 p.Pro103Ser

c.307C>T · VCV3574995

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3097 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Diamond-Blackfan anemia 10

Computational evidence

Protein change
AlphaMissense	0.3097	likely benign
REVEL	0.702	pathogenic-leaning
SaProt	LLR -11.85	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.40	unconstrained · MANE · 1,984 bp · p 4.7e-14 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,906 alleles

Overall 6.2e-05% 1/1,613,774 alleles · very rare exomes 1/1,461,654 · genomes 0/152,120 · joint denominator

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.Pro103Ser
Coding: c.307C>T
MANE Select: NM_001029
Type: single nucleotide variant
Location: chr12:56043488 (GRCh38)
Gene constraint: LOEUF 0.32 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 86.09 · 185 PDB
Residue 103: the 'disordered' region

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 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
RPS26 c.312+3G>A Uncertain significance ★★ 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-pro103ser (accessed [today's date]).

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