Is RPL35A p.Phe11= (c.33T>C) pathogenic?

RPL35A p.Phe11= (c.33T>C) is classified Likely benign in RPL35A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-09). Very rare (popmax 8.47e-05%, nfe); Associated with Diamond-Blackfan anemia 5.

What condition is associated with RPL35A p.Phe11= (c.33T>C)?

RPL35A p.Phe11= (c.33T>C) is associated with Diamond-Blackfan anemia 5 (ClinVar).

How common is RPL35A p.Phe11= (c.33T>C) in the general population?

RPL35A p.Phe11= (c.33T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Diamond-Blackfan anemia inherited?

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

RPL35A p.Phe11=

c.33T>C · rs751752645 · VCV1614741

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	phastCons 1
Overall
CADD	13.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,042 alleles

Overall 0.000124% 2/1,614,240 alleles · very rare exomes 2/1,461,882 · genomes 0/152,358 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)grpmax	8.47e-05%	1,180,043

Remaining individuals 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: RPL35A
Protein: p.Phe11=
Coding: c.33T>C
MANE Select: NM_000996
dbSNP: rs751752645
Type: single nucleotide variant
Location: chr3:197951180 (GRCh38)
Gene constraint: LOEUF 0.202 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 95.78 · 183 PDB
Residue 11: a β-strand

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)

Similar variants

RPL35A p.Arg85Cys Uncertain significance ★★ ⚠ same condition
RPL35A p.Gly62Ser Uncertain significance ★★ ⚠ same condition
RPL35A p.Arg109= Likely benign ★★ 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.Arg19= Likely benign ★ same condition
RPL35A p.Gly62Cys 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-phe11 (accessed [today's date]).

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