Is RRM2B p.Asp178= (c.534T>C) pathogenic?

RRM2B p.Asp178= (c.534T>C) is classified Likely benign in RRM2B (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-11-19). Very rare (popmax 0.000372%); Associated with rod-cone dystrophy, sensorineural deafness, and Fanconi-type renal dysfunction.

What condition is associated with RRM2B p.Asp178= (c.534T>C)?

RRM2B p.Asp178= (c.534T>C) is associated with rod-cone dystrophy, sensorineural deafness, and Fanconi-type renal dysfunction, mitochondrial DNA depletion syndrome 8a, progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5 (ClinVar).

How common is RRM2B p.Asp178= (c.534T>C) in the general population?

RRM2B p.Asp178= (c.534T>C) is very rare (popmax 0.000372%) (gnomAD).

RRM2B p.Asp178=

c.534T>C · rs1810881397 · VCV1566332

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000372%)

Conditions

rod-cone dystrophy, sensorineural deafness, and Fanconi-type renal dysfunction

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -0.82, phastCons 1
Overall
CADD	7.881	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000372%

Overall 0.000372% 6/1,612,286 alleles · very rare exomes 6/1,459,918 · genomes 0/152,368 · joint denominator

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.Asp178=
Coding: c.534T>C
MANE Select: NM_015713
dbSNP: rs1810881397
Type: single nucleotide variant
Location: chr8:102224062 (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

Disease context

rod-cone dystrophy, sensorineural deafness, and Fanconi-type renal dysfunction — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mitochondrial DNA depletion syndrome 8a progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5

Similar variants

RRM2B p.Asp178Gly Uncertain significance ★ ⚠ same residue
RRM2B c.322-2A>G Pathogenic ★★ same condition
RRM2B c.455+1G>A Likely pathogenic ★★ same condition
RRM2B p.Arg110Cys Likely pathogenic ★★ same condition
RRM2B p.Arg174Ter Pathogenic/Likely pathogenic ★★ same condition
RRM2B p.Arg327Ter Pathogenic ★★ same condition
RRM2B p.Arg41Trp Pathogenic/Likely pathogenic ★★ same condition
RRM2B p.Gly229Val Pathogenic/Likely pathogenic ★★ 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/rrm2b-p-asp178 (accessed [today's date]).

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