Is RPS10 p.Ala115Val (c.344C>T) pathogenic?

RPS10 p.Ala115Val (c.344C>T) is classified Uncertain significance in RPS10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-06). AlphaMissense: likely benign (0.1538); Very rare (popmax 0.00439%, sas); Associated with Diamond-Blackfan anemia.

What condition is associated with RPS10 p.Ala115Val (c.344C>T)?

RPS10 p.Ala115Val (c.344C>T) is associated with Diamond-Blackfan anemia (ClinVar).

How common is RPS10 p.Ala115Val (c.344C>T) in the general population?

RPS10 p.Ala115Val (c.344C>T) is very rare (popmax 0.00439%, sas) (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.Ala115Val (c.344C>T)?

AlphaMissense predicts likely benign (score 0.1538) — an in-silico prediction, not a clinical call.

RPS10 p.Ala115Val

c.344C>T · rs774624551 · VCV2912518

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1538 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Diamond-Blackfan anemia

Computational evidence

Protein change
AlphaMissense	0.1538	likely benign
REVEL	0.422	indeterminate
SaProt	LLR -7.58	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.7	GERP 0.94, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 7,712 bp · p 1.1e-08 · regional, not allelic
Overall
CADD	26.1	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 0.00439% South Asian · 4/91,070 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00242% 39/1,613,682 alleles · very rare exomes 36/1,461,650 · genomes 3/152,032 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00938%	10,666
South Asiangrpmax	0.00439%	22,767
Remaining individualsnot grpmax-eligible	0.0032%	31,235
European (non-Finnish)	0.0022%	45,379
African / African-American	0.00134%	74,858

Finnish 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.Ala115Val
Coding: c.344C>T
MANE Select: NM_001014
dbSNP: rs774624551
Type: single nucleotide variant
Location: chr6:34421786 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 75.34 · 195 PDB
Residue 115: 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.Ala115= Likely benign ★★ same residue
RPS10-NUDT3 p.Ala115Glu Uncertain significance ★ ⚠ same residue
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

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-ala115val (accessed [today's date]).

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