Is NMUR2 p.Arg333Cys (c.997C>T) pathogenic?

NMUR2 p.Arg333Cys (c.997C>T) is classified Uncertain significance in NMUR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-20). AlphaMissense: likely benign (0.3053); Ultra-rare (popmax 0.0334%, eas).

How common is NMUR2 p.Arg333Cys (c.997C>T) in the general population?

NMUR2 p.Arg333Cys (c.997C>T) is ultra-rare (popmax 0.0334%, eas) (gnomAD).

What do computational predictors say about NMUR2 p.Arg333Cys (c.997C>T)?

AlphaMissense predicts likely benign (score 0.3053) — an in-silico prediction, not a clinical call.

NMUR2 p.Arg333Cys

c.997C>T · rs368160909 · VCV2238869

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3053 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3053	likely benign
REVEL	0.25	benign-leaning
SaProt	LLR -11.13	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.1	GERP 1.7, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 13 kb · p 0.37 · regional, not allelic
Overall
CADD	28.6	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 0.0334% East Asian · 15/44,886 alleles

Filtering AF 0.0206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0166%

Overall 0.00353% 57/1,613,890 alleles · ultra-rare exomes 49/1,461,740 · genomes 8/152,150 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0334%	2,992
Middle Eastern	0.0329%	3,042
African / African-American	0.0174%	5,762
Remaining individualsnot grpmax-eligible	0.0032%	31,245
South Asian	0.0022%	45,538
European (non-Finnish)	0.00186%	53,633
Admixed American	0.00167%	59,984

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: NMUR2
Protein: p.Arg333Cys
Coding: c.997C>T
MANE Select: NM_020167
dbSNP: rs368160909
Type: single nucleotide variant
Location: chr5:152392442 (GRCh38)
Gene constraint: LOEUF 1.327 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.92 · 3 PDB
Residue 333: an α-helix

Full NMUR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NMUR2 p.Ala124Val Uncertain significance ★ ⚠ same type
NMUR2 p.Ala132Val Uncertain significance ★ ⚠ same type
NMUR2 p.Ala147Thr Uncertain significance ★ same type
NMUR2 p.Ala154Val Uncertain significance ★ ⚠ same type
NMUR2 p.Ala395Glu Uncertain significance ★ ⚠ same type
NMUR2 p.Arg108His Uncertain significance ★ ⚠ same type
NMUR2 p.Arg153Leu Uncertain significance ★ ⚠ same type
NMUR2 p.Arg162Trp 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/nmur2-p-arg333cys (accessed [today's date]).

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