Is RPL35A p.Arg109= (c.327G>A) pathogenic?

RPL35A p.Arg109= (c.327G>A) is classified Likely benign in RPL35A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-05-28). Very rare (popmax 0.00426%, nfe); Associated with Diamond-Blackfan anemia.

What condition is associated with RPL35A p.Arg109= (c.327G>A)?

RPL35A p.Arg109= (c.327G>A) is associated with Diamond-Blackfan anemia, Diamond-Blackfan anemia 5 (ClinVar).

How common is RPL35A p.Arg109= (c.327G>A) in the general population?

RPL35A p.Arg109= (c.327G>A) is very rare (popmax 0.00426%, nfe) (gnomAD).

How is Diamond-Blackfan anemia inherited?

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

RPL35A p.Arg109=

c.327G>A · rs754407977 · VCV1653086

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00426%, nfe)

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 0.77	phastCons 1
Overall
CADD	7.224	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00426% European (non-Finnish) · 50/1,174,866 alleles

Filtering AF 0.00327% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.0033% 53/1,606,270 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00426%	23,497
Remaining individualsnot grpmax-eligible	0.00322%	31,058
Admixed American	0.00167%	59,984

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: RPL35A
Protein: p.Arg109=
Coding: c.327G>A
MANE Select: NM_000996
dbSNP: rs754407977
Type: single nucleotide variant
Location: chr3:197955767 (GRCh38)
Gene constraint: LOEUF 0.202 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 95.78 · 183 PDB

Full RPL35A 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

Also linked: Diamond-Blackfan anemia 5

For Diamond-Blackfan anemia (Orphanet):

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

Similar variants

RPL35A p.Arg85Cys Uncertain significance ★★ ⚠ same condition
RPL35A p.Gly62Ser Uncertain significance ★★ ⚠ same condition
RPL35A c.12-5C>G Conflicting classifications of pathogenicity ★ same condition
RPL35A p.Asp37Asn Uncertain significance ★ ⚠ same condition
RPL35A p.Glu31Asp Uncertain significance ★ ⚠ same condition
RPL35A p.Val84Asp Uncertain significance ★ ⚠ same condition
RPL35A p.Ala77= Likely benign ★ same condition
RPL35A p.Arg19= 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/rpl35a-p-arg109 (accessed [today's date]).

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