Is NMUR1 p.Arg259Trp (c.775C>T) pathogenic?

NMUR1 p.Arg259Trp (c.775C>T) is classified Benign/Likely benign in NMUR1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-04-01). AlphaMissense: likely benign (0.0935); Low-frequency (popmax 2.01%, mid).

How common is NMUR1 p.Arg259Trp (c.775C>T) in the general population?

NMUR1 p.Arg259Trp (c.775C>T) is low-frequency (popmax 2.01%, mid) (gnomAD).

What do computational predictors say about NMUR1 p.Arg259Trp (c.775C>T)?

AlphaMissense predicts likely benign (score 0.0935) — an in-silico prediction, not a clinical call.

NMUR1 p.Arg259Trp

c.775C>T · rs150482580 · VCV775190

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0935 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.01%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0935	likely benign
REVEL	0.113	moderately benign-leaning
SaProt	LLR -8.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -0.53, phastCons 0.49
Regional constraint	o/e 0.91	unconstrained · MANE · 5,315 bp · p 0.033 · regional, not allelic
Overall
CADD	18.36	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 2.01% Middle Eastern · 120/5,970 alleles

Filtering AF 1.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.61%

Overall 0.593% 9,571/1,613,780 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	2.01%	50
Finnishnot grpmax-eligible	1.13%	89
Ashkenazi Jewishnot grpmax-eligible	0.95%	105
European (non-Finnish)	0.632%	158
Remaining individualsnot grpmax-eligible	0.613%	163
Amishnot grpmax-eligible	0.548%	182
Admixed American	0.368%	272
South Asian	0.345%	290
African / African-American	0.0893%	1,120
East Asian	0.00223%	44,888

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.Arg259Trp
Coding: c.775C>T
MANE Select: NM_006056
dbSNP: rs150482580
Type: single nucleotide variant
Location: chr2:231528246 (GRCh38)
Gene constraint: LOEUF 1.399 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.23 · 2 PDB
Residue 259: an α-helix

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

Similar variants

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
NMUR1 p.Arg175Trp 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-arg259trp (accessed [today's date]).

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