Is RPL26 p.Lys89= (c.267G>A) pathogenic?

RPL26 p.Lys89= (c.267G>A) is classified Likely benign in RPL26 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-28). Ultra-rare (popmax 0.016%, afr); Associated with Diamond-Blackfan anemia 11.

What condition is associated with RPL26 p.Lys89= (c.267G>A)?

RPL26 p.Lys89= (c.267G>A) is associated with Diamond-Blackfan anemia 11, Diamond-Blackfan anemia (ClinVar).

How common is RPL26 p.Lys89= (c.267G>A) in the general population?

RPL26 p.Lys89= (c.267G>A) is ultra-rare (popmax 0.016%, afr) (gnomAD).

How is Diamond-Blackfan anemia inherited?

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

RPL26 p.Lys89=

c.267G>A · VCV3767087

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Conditions

Diamond-Blackfan anemia 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.5	GERP -0.43, phastCons 1
Overall
CADD	10.97	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.016% African / African-American · 12/74,914 alleles

Filtering AF 0.00922% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.00118% 19/1,613,734 alleles · ultra-rare exomes 12/1,461,580 · genomes 7/152,154 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,243
Admixed American	0.01%	9,992
European (non-Finnish)	8.48e-05%	1,179,934

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: RPL26
Protein: p.Lys89=
Coding: c.267G>A
MANE Select: NM_000987
Type: single nucleotide variant
Location: chr17:8379838 (GRCh38)
Gene constraint: LOEUF 0.258 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 92.77 · 186 PDB

Full RPL26 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Diamond-Blackfan anemia 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Diamond-Blackfan anemia

For Diamond-Blackfan anemia (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

RPL26 c.-5-2A>G Likely pathogenic ★★ same condition
RPL26 p.Arg126His Uncertain significance ★★ ⚠ same condition
RPL26 c.168+17G>A Benign/Likely benign ★★ same condition
RPL26 p.Asn43Ser Likely benign ★★ ⚠ same condition
RPL26 p.Asp114= Likely benign ★★ same condition
RPL26 p.His100= Likely benign ★★ same condition
RPL26 p.His24= Likely benign ★★ same condition
RPL26 p.His96= Likely benign ★★ 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/rpl26-p-lys89 (accessed [today's date]).

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