Is NMUR2 p.Pro324Leu (c.971C>T) pathogenic?

NMUR2 p.Pro324Leu (c.971C>T) is classified Uncertain significance in NMUR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). AlphaMissense: likely pathogenic (0.8885); Absent from gnomAD v4.1.

How common is NMUR2 p.Pro324Leu (c.971C>T) in the general population?

NMUR2 p.Pro324Leu (c.971C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NMUR2 p.Pro324Leu (c.971C>T)?

AlphaMissense predicts likely pathogenic (score 0.8885) — an in-silico prediction, not a clinical call.

NMUR2 p.Pro324Leu

c.971C>T · VCV4558306

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8885 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8885	likely pathogenic · top 6% in NMUR2
REVEL	0.97	strongly pathogenic-leaning
SaProt	LLR -13.83	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 13 kb · p 0.37 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NMUR2
Protein: p.Pro324Leu
Coding: c.971C>T
MANE Select: NM_020167
Type: single nucleotide variant
Location: chr5:152392468 (GRCh38)
Gene constraint: LOEUF 1.327 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.92 · 3 PDB
Residue 324: an α-helix

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

Similar variants

NMUR2 p.Pro324= Benign ★ same residue
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

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-pro324leu (accessed [today's date]).

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