Is RPS7 p.Pro136Ala (c.406C>G) pathogenic?

RPS7 p.Pro136Ala (c.406C>G) is classified Uncertain significance in RPS7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-15). AlphaMissense: likely pathogenic (0.9965); Absent from gnomAD v4.1; Associated with Diamond-Blackfan anemia 8.

What condition is associated with RPS7 p.Pro136Ala (c.406C>G)?

RPS7 p.Pro136Ala (c.406C>G) is associated with Diamond-Blackfan anemia 8 (ClinVar).

How common is RPS7 p.Pro136Ala (c.406C>G) in the general population?

RPS7 p.Pro136Ala (c.406C>G) 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 RPS7 p.Pro136Ala (c.406C>G)?

AlphaMissense predicts likely pathogenic (score 0.9965) — an in-silico prediction, not a clinical call.

RPS7 p.Pro136Ala

c.406C>G · rs1661370560 · VCV855605

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9965 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Diamond-Blackfan anemia 8

Computational evidence

Protein change
AlphaMissense	0.9965	likely pathogenic
REVEL	0.796	moderately pathogenic-leaning
SaProt	LLR -11.73	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 7.3	GERP 2.2, phastCons 1
Regional constraint	o/e 0.43	unconstrained · MANE · 4,361 bp · p 1e-13 · regional, not allelic
Overall
CADD	24.3	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: RPS7
Protein: p.Pro136Ala
Coding: c.406C>G
MANE Select: NM_001011
dbSNP: rs1661370560
Type: single nucleotide variant
Location: chr2:3580159 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 87.04 · 182 PDB
Residue 136: a turn

Full RPS7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Diamond-Blackfan anemia 8 — 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

RPS7 c.75+1G>A Pathogenic ★★ same condition
RPS7 c.356+6T>C Uncertain significance ★★ same condition
RPS7 c.-27C>T Uncertain significance ★★ same condition
RPS7 p.Ala26Val Uncertain significance ★★ ⚠ same condition
RPS7 p.Ala38Val Uncertain significance ★★ ⚠ same condition
RPS7 p.Arg145His Uncertain significance ★★ ⚠ same condition
RPS7 p.Arg152Pro Uncertain significance ★★ ⚠ same condition
RPS7 p.Asn12Ser Uncertain significance ★★ ⚠ 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/rps7-p-pro136ala (accessed [today's date]).

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