Is RPS26 p.Val69= (c.207G>C) pathogenic?

RPS26 p.Val69= (c.207G>C) is classified Likely benign in RPS26 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-03). Ultra-rare (popmax 0.0207%, mid); Associated with Diamond-Blackfan anemia 10.

What condition is associated with RPS26 p.Val69= (c.207G>C)?

RPS26 p.Val69= (c.207G>C) is associated with Diamond-Blackfan anemia 10 (ClinVar).

How common is RPS26 p.Val69= (c.207G>C) in the general population?

RPS26 p.Val69= (c.207G>C) is ultra-rare (popmax 0.0207%, mid) (gnomAD).

How is Diamond-Blackfan anemia inherited?

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

RPS26 p.Val69=

c.207G>C · rs776240183 · VCV1551609

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0207%, mid)

Conditions

Diamond-Blackfan anemia 10

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 4.1	GERP 1, phastCons 1
Overall
CADD	11.14	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0207% Middle Eastern · 1/4,824 alleles

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

Overall 0.000411% 6/1,459,610 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0207%	4,824
Admixed American	0.00167%	59,994
European (non-Finnish)	0.000339%	294,849

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: RPS26
Protein: p.Val69=
Coding: c.207G>C
MANE Select: NM_001029
dbSNP: rs776240183
Type: single nucleotide variant
Location: chr12:56043388 (GRCh38)
Gene constraint: LOEUF 0.32 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 86.09 · 185 PDB
Residue 69: a β-strand

Full RPS26 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Diamond-Blackfan anemia 10 — 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

RPS26 c.3+1G>T Pathogenic/Likely pathogenic ★★ same condition
RPS26 c.3+2T>G Likely pathogenic ★★ same condition
RPS26 p.Arg28Ter Pathogenic ★★ same condition
RPS26 p.Arg87Ter Pathogenic ★★ same condition
RPS26 p.Gln19Ter Pathogenic/Likely pathogenic ★★ same condition
RPS26 p.Met1Thr Pathogenic ★★ same condition
RPS26 p.Met1Val Pathogenic ★★ same condition
RPS26 c.312+3G>A 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/rps26-p-val69 (accessed [today's date]).

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