Is NMUR2 p.Arg41Pro (c.122G>C) pathogenic?

NMUR2 p.Arg41Pro (c.122G>C) is classified Uncertain significance in NMUR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-15). AlphaMissense: ambiguous (0.4785); Very rare (popmax 0.000339%, nfe).

How common is NMUR2 p.Arg41Pro (c.122G>C) in the general population?

NMUR2 p.Arg41Pro (c.122G>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about NMUR2 p.Arg41Pro (c.122G>C)?

AlphaMissense predicts ambiguous (score 0.4785) — an in-silico prediction, not a clinical call.

NMUR2 p.Arg41Pro

c.122G>C · rs779708928 · VCV2249591

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4785 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4785	ambiguous
REVEL	0.309	indeterminate
SaProt	LLR -12.61	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 1.7, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 13 kb · p 0.37 · regional, not allelic
Overall
CADD	24.3	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 0.000339% European (non-Finnish) · 4/1,179,952 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,898 alleles · very rare exomes 4/1,461,890 · genomes 0/152,008 · 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: NMUR2
Protein: p.Arg41Pro
Coding: c.122G>C
MANE Select: NM_020167
dbSNP: rs779708928
Type: single nucleotide variant
Location: chr5:152404992 (GRCh38)
Gene constraint: LOEUF 1.327 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.92 · 3 PDB

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-arg41pro (accessed [today's date]).

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