Is RPL35A p.Val84Asp (c.251T>A) pathogenic?

RPL35A p.Val84Asp (c.251T>A) is classified Uncertain significance in RPL35A (ClinVar, Single submitter, 1 submitter; last evaluated 2017-07-01). AlphaMissense: likely pathogenic (0.999); Absent from gnomAD v4.1; Associated with Diamond-Blackfan anemia.

What condition is associated with RPL35A p.Val84Asp (c.251T>A)?

RPL35A p.Val84Asp (c.251T>A) is associated with Diamond-Blackfan anemia (ClinVar).

How common is RPL35A p.Val84Asp (c.251T>A) in the general population?

RPL35A p.Val84Asp (c.251T>A) is absent from gnomAD v4.1 (gnomAD).

How is Diamond-Blackfan anemia inherited?

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

What do computational predictors say about RPL35A p.Val84Asp (c.251T>A)?

AlphaMissense predicts likely pathogenic (score 0.999) — an in-silico prediction, not a clinical call.

RPL35A p.Val84Asp

c.251T>A · rs2530431509 · VCV1792520

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Diamond-Blackfan anemia

Computational evidence

Protein change
AlphaMissense	0.999	likely pathogenic · top 5% in RPL35A
REVEL	0.945	strongly pathogenic-leaning
SaProt	LLR -15.91	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 4,802 bp · p 5.1e-05 · regional, not allelic
Overall
CADD	29.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RPL35A
Protein: p.Val84Asp
Coding: c.251T>A
MANE Select: NM_000996
dbSNP: rs2530431509
Type: single nucleotide variant
Location: chr3:197954089 (GRCh38)
Gene constraint: LOEUF 0.202 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 95.78 · 183 PDB
Residue 84: a β-strand

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

For Diamond-Blackfan anemia (Orphanet):

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

Similar variants

RPL35A p.Arg109= Likely benign ★★ same condition
RPL35A c.12-5C>G Conflicting classifications of pathogenicity ★ same condition
RPL35A p.Ala77= Likely benign ★ same condition
RPL35A p.Arg85Cys Uncertain significance ★★ ⚠ same type
RPL35A p.Gly62Ser Uncertain significance ★★ ⚠ same type
RPL35A p.Asp37Asn Uncertain significance ★ ⚠ same type
RPL35A p.Glu31Asp Uncertain significance ★ ⚠ same type
RPL35A p.Arg19= Likely benign ★ same type

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-val84asp (accessed [today's date]).

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