Is RPL35A p.Ser7= (c.21C>T) pathogenic?

RPL35A p.Ser7= (c.21C>T) is classified Benign/Likely benign in RPL35A (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-12-23). Rare (popmax 0.615%, eas); Associated with Diamond-Blackfan anemia 5.

What condition is associated with RPL35A p.Ser7= (c.21C>T)?

RPL35A p.Ser7= (c.21C>T) is associated with Diamond-Blackfan anemia 5, Diamond-Blackfan anemia (ClinVar).

How common is RPL35A p.Ser7= (c.21C>T) in the general population?

RPL35A p.Ser7= (c.21C>T) is rare (popmax 0.615%, eas) (gnomAD).

How is Diamond-Blackfan anemia inherited?

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

RPL35A p.Ser7=

c.21C>T · rs145660527 · VCV344528

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.615%, eas)

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
Constraint at this position
Conservation	phyloP 1.8	phastCons 1
Overall
CADD	13.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.615% East Asian · 276/44,886 alleles

Filtering AF 0.555% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.532%

Overall 0.0182% 293/1,614,016 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.615%	163
Remaining individualsnot grpmax-eligible	0.0128%	7,813
South Asian	0.00329%	30,359
African / African-American	0.00133%	74,958
European (non-Finnish)	0.000424%	236,004

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.Ser7=
Coding: c.21C>T
MANE Select: NM_032263 · reported on NM_000996
dbSNP: rs145660527
Type: single nucleotide variant
Location: chr3:197951168 (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

Also linked: Diamond-Blackfan anemia

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-ser7 (accessed [today's date]).

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