Is NMUR2 p.Arg162Trp (c.484C>T) pathogenic?

NMUR2 p.Arg162Trp (c.484C>T) is classified Uncertain significance in NMUR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). AlphaMissense: likely benign (0.1643); Very rare (popmax 0.00441%, nfe).

How common is NMUR2 p.Arg162Trp (c.484C>T) in the general population?

NMUR2 p.Arg162Trp (c.484C>T) is very rare (popmax 0.00441%, nfe) (gnomAD).

What do computational predictors say about NMUR2 p.Arg162Trp (c.484C>T)?

AlphaMissense predicts likely benign (score 0.1643) — an in-silico prediction, not a clinical call.

NMUR2 p.Arg162Trp

c.484C>T · rs374625926 · VCV2597242

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1643 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00441%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1643	likely benign
REVEL	0.423	indeterminate
SaProt	LLR -9.55	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.94	GERP -3.7, phastCons 0.37
Regional constraint	o/e 1.04	unconstrained · MANE · 13 kb · p 0.37 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00441% European (non-Finnish) · 52/1,180,016 alleles

Filtering AF 0.00342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00359% 58/1,613,958 alleles · very rare exomes 53/1,461,842 · genomes 5/152,116 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00469%	21,340
European (non-Finnish)grpmax	0.00441%	22,693
Admixed American	0.00167%	60,004
Remaining individualsnot grpmax-eligible	0.0016%	62,484
African / African-American	0.00134%	74,904

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg162Trp
Coding: c.484C>T
MANE Select: NM_020167
dbSNP: rs374625926
Type: single nucleotide variant
Location: chr5:152404630 (GRCh38)
Gene constraint: LOEUF 1.327 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.92 · 3 PDB
Residue 162: 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.Arg333Cys 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-arg162trp (accessed [today's date]).

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