Is RPS10 p.Pro30Leu (c.89C>T) pathogenic?

RPS10 p.Pro30Leu (c.89C>T) is classified Uncertain significance in RPS10 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-08-22). AlphaMissense: ambiguous (0.3655); Very rare (popmax 0.00593%, nfe); Associated with Diamond-Blackfan anemia 9.

What condition is associated with RPS10 p.Pro30Leu (c.89C>T)?

RPS10 p.Pro30Leu (c.89C>T) is associated with Diamond-Blackfan anemia 9, Diamond-Blackfan anemia (ClinVar).

How common is RPS10 p.Pro30Leu (c.89C>T) in the general population?

RPS10 p.Pro30Leu (c.89C>T) is very rare (popmax 0.00593%, 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 RPS10 p.Pro30Leu (c.89C>T)?

AlphaMissense predicts ambiguous (score 0.3655) — an in-silico prediction, not a clinical call.

RPS10 p.Pro30Leu

c.89C>T · rs755445102 · VCV997511

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.3655 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00593%, nfe)

Conditions

Diamond-Blackfan anemia 9

Computational evidence

Protein change
AlphaMissense	0.3655	ambiguous
REVEL	0.598	indeterminate
SaProt	LLR -13.29	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 7,712 bp · p 1.1e-08 · regional, not allelic
Overall
CADD	33.0	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 0.00593% European (non-Finnish) · 70/1,179,956 alleles

Filtering AF 0.00478% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00439%

Overall 0.00471% 76/1,613,316 alleles · very rare exomes 71/1,461,250 · genomes 5/152,066 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00593%	16,857
Admixed American	0.005%	19,997
Remaining individualsnot grpmax-eligible	0.00481%	20,811

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: RPS10
Protein: p.Pro30Leu
Coding: c.89C>T
MANE Select: NM_001014
dbSNP: rs755445102
Type: single nucleotide variant
Location: chr6:34425133 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 75.34 · 195 PDB
Residue 30: a β-strand

Full RPS10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Diamond-Blackfan anemia 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Diamond-Blackfan anemia

For Diamond-Blackfan anemia (Orphanet):

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

Similar variants

RPS10 p.Arg113Ter Pathogenic ★★ same condition
RPS10 c.322+3A>G Uncertain significance ★★ same condition
RPS10 p.Arg158His Uncertain significance ★★ ⚠ same condition
RPS10 p.Arg55Gln Uncertain significance ★★ same condition
RPS10 p.Arg8Trp Uncertain significance ★★ ⚠ same condition
RPS10 p.Arg96Cys Uncertain significance ★★ ⚠ same condition
RPS10 p.Arg98His Uncertain significance ★★ ⚠ same condition
RPS10 p.Asp137Asn 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/rps10-p-pro30leu (accessed [today's date]).

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