Is NMUR1 p.Arg87Cys (c.259C>T) pathogenic?

NMUR1 p.Arg87Cys (c.259C>T) is classified Uncertain significance in NMUR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-26). AlphaMissense: likely benign (0.0904); Rare (popmax 0.104%, nfe).

How common is NMUR1 p.Arg87Cys (c.259C>T) in the general population?

NMUR1 p.Arg87Cys (c.259C>T) is rare (popmax 0.104%, nfe) (gnomAD).

What do computational predictors say about NMUR1 p.Arg87Cys (c.259C>T)?

AlphaMissense predicts likely benign (score 0.0904) — an in-silico prediction, not a clinical call.

NMUR1 p.Arg87Cys

c.259C>T · rs141558874 · VCV3200864

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0904 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.104%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0904	likely benign
REVEL	0.144	moderately benign-leaning
SaProt	LLR -10.92	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.87	GERP -2, phastCons 0.19
Regional constraint	o/e 0.91	unconstrained · MANE · 5,315 bp · p 0.033 · regional, not allelic
Overall
CADD	18.69	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.104% European (non-Finnish) · 1,231/1,180,040 alleles

Filtering AF 0.0994% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0975%

Overall 0.0847% 1,367/1,614,212 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.104%	959
Admixed American	0.09%	1,112
Remaining individualsnot grpmax-eligible	0.0848%	1,179
African / African-American	0.024%	4,170
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,921
South Asian	0.00329%	30,361
Finnishnot grpmax-eligible	0.00312%	32,011
East Asian	0.00223%	44,882

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: NMUR1
Protein: p.Arg87Cys
Coding: c.259C>T
MANE Select: NM_006056
dbSNP: rs141558874
Type: single nucleotide variant
Location: chr2:231528762 (GRCh38)
Gene constraint: LOEUF 1.399 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.23 · 2 PDB
Residue 87: an α-helix

Full NMUR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NMUR1 p.Arg259Trp Benign/Likely benign ★★ same type
NMUR1 p.Ala176Val Uncertain significance ★ ⚠ same type
NMUR1 p.Ala236Val Uncertain significance ★ ⚠ same type
NMUR1 p.Ala25Thr Uncertain significance ★ ⚠ same type
NMUR1 p.Ala269Val Uncertain significance ★ ⚠ same type
NMUR1 p.Ala350Val Uncertain significance ★ ⚠ same type
NMUR1 p.Ala412Ser Uncertain significance ★ ⚠ same type
NMUR1 p.Arg159His 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/nmur1-p-arg87cys (accessed [today's date]).

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