Is RRM2B p.Ter352= (c.*4dup) pathogenic?

RRM2B p.Ter352= (c.4dup) is classified Likely benign in RRM2B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-03-16). Very rare (popmax 0.00167%, amr).

How common is RRM2B p.Ter352= (c.*4dup) in the general population?

RRM2B p.Ter352= (c.*4dup) is very rare (popmax 0.00167%, amr) (gnomAD).

RRM2B p.Ter352=

c.*4dup · rs1314882154 · VCV559373

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.082	GERP -2.5
Overall
CADD	5.187	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,916 alleles

Filtering AF 0.00069% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00054%

Overall 0.000931% 15/1,610,332 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,916
European (non-Finnish)	0.00119%	84,081

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.Ter352=
Coding: c.*4dup
MANE Select: NM_015713
dbSNP: rs1314882154
Type: Duplication
Location: chr8:102208128 (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.322-25_322-18dup Benign/Likely benign ★★ same type
RRM2B c.48+215dup Benign ★★ same type
RRM2B c.48+108_48+111dup Uncertain significance ★ same type
RRM2B c.204+263dup Benign ★ same type
RRM2B c.684+72dup Benign ★ same type
RRM2B c.904-248dup Likely benign ★ same type
RRM2B p.Asn322fs Pathogenic same type
RRM2B c.48+97dup 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/rrm2b-p-ter352 (accessed [today's date]).

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