Is RPS10 p.Ala63= (c.189C>T) pathogenic?

RPS10 p.Ala63= (c.189C>T) is classified Likely benign in RPS10 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-17). Very rare (popmax 0.00667%, afr); Associated with Diamond-Blackfan anemia.

What condition is associated with RPS10 p.Ala63= (c.189C>T)?

RPS10 p.Ala63= (c.189C>T) is associated with Diamond-Blackfan anemia (ClinVar).

How common is RPS10 p.Ala63= (c.189C>T) in the general population?

RPS10 p.Ala63= (c.189C>T) is very rare (popmax 0.00667%, afr) (gnomAD).

How is Diamond-Blackfan anemia inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

RPS10 p.Ala63=

c.189C>T · rs772715124 · VCV1610227

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Conditions

Diamond-Blackfan anemia

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 0.22	GERP -1.1, phastCons 0.93
Overall
CADD	10.53	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% African / African-American · 5/74,916 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.0018% 29/1,613,962 alleles · very rare exomes 27/1,461,798 · genomes 2/152,164 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,983
Remaining individualsnot grpmax-eligible	0.0048%	20,829
European (non-Finnish)	0.00178%	56,192

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.Ala63=
Coding: c.189C>T
MANE Select: NM_001014
dbSNP: rs772715124
Type: single nucleotide variant
Location: chr6:34424802 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 75.34 · 195 PDB
Residue 63: a β-strand

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-ala63 (accessed [today's date]).

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