Is RPS10 p.Pro134Ser (c.400C>T) pathogenic?

RPS10 p.Pro134Ser (c.400C>T) is classified Uncertain significance in RPS10 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-02). AlphaMissense: likely benign (0.0903); Ultra-rare (popmax 0.0417%, amr); Associated with Diamond-Blackfan anemia.

What condition is associated with RPS10 p.Pro134Ser (c.400C>T)?

RPS10 p.Pro134Ser (c.400C>T) is associated with Diamond-Blackfan anemia (ClinVar).

How common is RPS10 p.Pro134Ser (c.400C>T) in the general population?

RPS10 p.Pro134Ser (c.400C>T) is ultra-rare (popmax 0.0417%, amr) (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.Pro134Ser (c.400C>T)?

AlphaMissense predicts likely benign (score 0.0903) — an in-silico prediction, not a clinical call.

RPS10 p.Pro134Ser

c.400C>T · rs759213353 · VCV965050

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0903 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0417%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Diamond-Blackfan anemia

Computational evidence

Protein change
AlphaMissense	0.0903	likely benign
REVEL	0.428	indeterminate
SaProt	LLR -8.39	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP -0.13, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 7,712 bp · p 1.1e-08 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0417% Admixed American · 25/59,972 alleles

Filtering AF 0.0289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0248%

Overall 0.00428% 69/1,613,588 alleles · ultra-rare exomes 64/1,461,516 · genomes 5/152,072 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0417%	2,399
Remaining individualsnot grpmax-eligible	0.00641%	15,613
European (non-Finnish)	0.00331%	30,253
South Asian	0.0011%	91,058

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.Pro134Ser
Coding: c.400C>T
MANE Select: NM_001014
dbSNP: rs759213353
Type: single nucleotide variant
Location: chr6:34421730 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 75.34 · 195 PDB
Residue 134: the 'disordered' region

Full RPS10 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

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.Arg98His Uncertain significance ★★ ⚠ same condition
RPS10 p.Asp137Asn Uncertain significance ★★ ⚠ same condition
RPS10 p.Gly111Ser 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-pro134ser (accessed [today's date]).

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