Is RPL35A p.Arg46= (c.138A>G) pathogenic?

RPL35A p.Arg46= (c.138A>G) is classified Uncertain significance in RPL35A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-20). Very rare (popmax 0.004%, afr); Associated with Diamond-Blackfan anemia 5.

What condition is associated with RPL35A p.Arg46= (c.138A>G)?

RPL35A p.Arg46= (c.138A>G) is associated with Diamond-Blackfan anemia 5 (ClinVar).

How common is RPL35A p.Arg46= (c.138A>G) in the general population?

RPL35A p.Arg46= (c.138A>G) is very rare (popmax 0.004%, afr) (gnomAD).

How is Diamond-Blackfan anemia inherited?

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

RPL35A p.Arg46=

c.138A>G · rs1348675711 · VCV2741212

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

Diamond-Blackfan anemia 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.38	gain · loss 0.09 · independent
Constraint at this position
Conservation	phyloP 1.3	phastCons 1
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,914 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,613,972 alleles · very rare

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.Arg46=
Coding: c.138A>G
MANE Select: NM_032263 · reported on NM_000996
dbSNP: rs1348675711
Type: single nucleotide variant
Location: chr3:197951285 (GRCh38)

Full RPL35A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Diamond-Blackfan anemia 5 — 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)

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-arg46 (accessed [today's date]).

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