Is RRM1 p.Ser20Pro (c.58T>C) pathogenic?

RRM1 p.Ser20Pro (c.58T>C) is classified Uncertain significance in RRM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-01). AlphaMissense: likely pathogenic (0.9781); Absent from gnomAD v4.1.

How common is RRM1 p.Ser20Pro (c.58T>C) in the general population?

RRM1 p.Ser20Pro (c.58T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RRM1 p.Ser20Pro (c.58T>C)?

AlphaMissense predicts likely pathogenic (score 0.9781) — an in-silico prediction, not a clinical call.

RRM1 p.Ser20Pro

c.58T>C · rs2498581340 · VCV2672455

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9781 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9781	likely pathogenic
REVEL	0.373	indeterminate
SaProt	LLR -15.02	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 12 kb · p 5.2e-12 · regional, not allelic
Overall
CADD	25.6	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: RRM1
Protein: p.Ser20Pro
Coding: c.58T>C
MANE Select: NM_001033
dbSNP: rs2498581340
Type: single nucleotide variant
Location: chr11:4102031 (GRCh38)
Gene constraint: LOEUF 0.242 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 92.43 · 12 PDB
Residue 20: the atp-cone domain; an α-helix

Full RRM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RRM1 p.Arg381His Likely pathogenic ★★ ⚠ same type
RRM1 p.Leu121= Benign ★★ same type
RRM1 p.Ala467Ser Uncertain significance ★ ⚠ same type
RRM1 p.Ala511Thr Uncertain significance ★ ⚠ same type
RRM1 p.Ala522Ser Uncertain significance ★ ⚠ same type
RRM1 p.Ala547Gly Uncertain significance ★ same type
RRM1 p.Arg130Cys Uncertain significance ★ ⚠ same type
RRM1 p.Arg212His 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/rrm1-p-ser20pro (accessed [today's date]).

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