Is RPS10 p.Ser97Arg (c.291C>G) pathogenic?

RPS10 p.Ser97Arg (c.291C>G) is classified Uncertain significance in RPS10 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-08). AlphaMissense: likely pathogenic (0.9837); Very rare (popmax 0.00133%, afr); Associated with Diamond-Blackfan anemia.

What condition is associated with RPS10 p.Ser97Arg (c.291C>G)?

RPS10 p.Ser97Arg (c.291C>G) is associated with Diamond-Blackfan anemia (ClinVar).

How common is RPS10 p.Ser97Arg (c.291C>G) in the general population?

RPS10 p.Ser97Arg (c.291C>G) is very rare (popmax 0.00133%, afr) (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.Ser97Arg (c.291C>G)?

AlphaMissense predicts likely pathogenic (score 0.9837) — an in-silico prediction, not a clinical call.

RPS10 p.Ser97Arg

c.291C>G · rs145746888 · VCV3023392

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9837 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Diamond-Blackfan anemia

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.9837	likely pathogenic
REVEL	0.293	indeterminate
SaProt	LLR -12.44	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.3	GERP -0.2, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 7,712 bp · p 1.1e-08 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00133% African / African-American · 1/74,944 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000867% 14/1,614,072 alleles · very rare exomes 12/1,461,830 · genomes 2/152,242 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,944
South Asian	0.0011%	91,084
European (non-Finnish)	0.00102%	98,337

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.Ser97Arg
Coding: c.291C>G
MANE Select: NM_001014
dbSNP: rs145746888
Type: single nucleotide variant
Location: chr6:34424700 (GRCh38)

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)

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-ser97arg (accessed [today's date]).

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