Is RPS20 p.Pro69Ser (c.205C>T) pathogenic?

RPS20 p.Pro69Ser (c.205C>T) is classified Uncertain significance in RPS20 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-29). AlphaMissense: likely pathogenic (0.9974); Very rare (popmax 0.0011%, sas).

How common is RPS20 p.Pro69Ser (c.205C>T) in the general population?

RPS20 p.Pro69Ser (c.205C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about RPS20 p.Pro69Ser (c.205C>T)?

AlphaMissense predicts likely pathogenic (score 0.9974) — an in-silico prediction, not a clinical call.

RPS20 p.Pro69Ser

c.205C>T · VCV4841903

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9974 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9974	likely pathogenic
REVEL	0.758	pathogenic-leaning
SaProt	LLR -14.27	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 12	GERP 2, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 1,290 bp · p 6.4e-11 · regional, not allelic
Overall
CADD	25.9	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

Grpmax group 0.0011% South Asian · 1/91,068 alleles

Overall 6.87e-05% 1/1,455,958 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: RPS20
Protein: p.Pro69Ser
Coding: c.205C>T
MANE Select: NM_001023
Type: single nucleotide variant
Location: chr8:56073245 (GRCh38)
Gene constraint: LOEUF 0.481 · pLI 0.97 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.86 · 194 PDB
Residue 69: a β-strand

Full RPS20 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RPS20 c.103+5G>A Uncertain significance ★★ same type
RPS20 c.3+5G>A Uncertain significance ★★ same type
RPS20 c.4-4A>G Uncertain significance ★★ same type
RPS20 c.-3G>T Uncertain significance ★★ same type
RPS20 p.Ala119Gly Uncertain significance ★★ ⚠ same type
RPS20 p.Ala16Thr Uncertain significance ★★ ⚠ same type
RPS20 p.Ala16Val Uncertain significance ★★ ⚠ same type
RPS20 p.Ala2Gly Uncertain significance ★★ ⚠ 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/rps20-p-pro69ser (accessed [today's date]).

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