Is RPS10 p.Ile11Val (c.31A>G) pathogenic?

RPS10 p.Ile11Val (c.31A>G) is classified Uncertain significance in RPS10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-25). AlphaMissense: likely benign (0.3237); Very rare (popmax 0.000339%, nfe); Associated with Diamond-Blackfan anemia 9.

What condition is associated with RPS10 p.Ile11Val (c.31A>G)?

RPS10 p.Ile11Val (c.31A>G) is associated with Diamond-Blackfan anemia 9 (ClinVar).

How common is RPS10 p.Ile11Val (c.31A>G) in the general population?

RPS10 p.Ile11Val (c.31A>G) is very rare (popmax 0.000339%, 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.Ile11Val (c.31A>G)?

AlphaMissense predicts likely benign (score 0.3237) — an in-silico prediction, not a clinical call.

RPS10 p.Ile11Val

c.31A>G · VCV3593519

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3237 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Diamond-Blackfan anemia 9

Computational evidence

Protein change
AlphaMissense	0.3237	likely benign
REVEL	0.597	indeterminate
SaProt	LLR -11.22	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 0.93, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 7,712 bp · p 1.1e-08 · regional, not allelic
Overall
CADD	28.1	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 0.000339% European (non-Finnish) · 4/1,179,692 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,613,068 alleles · very rare exomes 5/1,460,840 · genomes 0/152,228 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)grpmax	0.000339%	294,923

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile11Val
Coding: c.31A>G
MANE Select: NM_001014
Type: single nucleotide variant
Location: chr6:34425191 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 75.34 · 195 PDB
Residue 11: an α-helix

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

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.Arg8Trp Uncertain significance ★★ ⚠ same condition
RPS10 p.Arg96Cys Uncertain significance ★★ ⚠ same condition
RPS10 p.Gly111Ser Uncertain significance ★★ ⚠ same condition
RPS10 p.Gly161Cys Uncertain significance ★★ ⚠ same condition
RPS10 p.Leu14Phe 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-ile11val (accessed [today's date]).

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