Is RRM2B p.Ser72Pro (c.214T>C) pathogenic?

RRM2B p.Ser72Pro (c.214T>C) is classified Uncertain significance in RRM2B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-02). AlphaMissense: likely pathogenic (0.8129); Very rare (popmax 0.00224%, eas).

How common is RRM2B p.Ser72Pro (c.214T>C) in the general population?

RRM2B p.Ser72Pro (c.214T>C) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about RRM2B p.Ser72Pro (c.214T>C)?

AlphaMissense predicts likely pathogenic (score 0.8129) — an in-silico prediction, not a clinical call.

RRM2B p.Ser72Pro

c.214T>C · rs764631345 · VCV1507828

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8129 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8129	likely pathogenic
REVEL	0.977	strongly pathogenic-leaning
SaProt	LLR -14.19	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 19 kb · p 0.00015 · regional, not allelic
Overall
CADD	28.2	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 0.00224% East Asian · 1/44,720 alleles

Overall 0.000125% 2/1,599,606 alleles · very rare exomes 2/1,447,292 · genomes 0/152,314 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,720
European (non-Finnish)	8.57e-05%	1,166,931

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: RRM2B
Protein: p.Ser72Pro
Coding: c.214T>C
MANE Select: NM_015713
dbSNP: rs764631345
Type: single nucleotide variant
Location: chr8:102226025 (GRCh38)
Gene constraint: LOEUF 0.688 · pLI 0.27 (gnomAD)
Structure: AlphaFold pLDDT 85.73 · 3 PDB

Full RRM2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RRM2B c.322-2A>G Pathogenic ★★ same type
RRM2B c.455+1G>A Likely pathogenic ★★ same type
RRM2B p.Arg110Cys Likely pathogenic ★★ same type
RRM2B p.Arg174Ter Pathogenic/Likely pathogenic ★★ same type
RRM2B p.Arg327Ter Pathogenic ★★ same type
RRM2B p.Arg41Trp Pathogenic/Likely pathogenic ★★ same type
RRM2B p.Gly229Val Pathogenic/Likely pathogenic ★★ same type
RRM2B p.Ile224Ser Pathogenic/Likely pathogenic ★★ 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/rrm2b-p-ser72pro (accessed [today's date]).

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