Is NMUR2 p.Met239Leu (c.715A>T) pathogenic?

NMUR2 p.Met239Leu (c.715A>T) is classified Uncertain significance in NMUR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.3131); Ultra-rare (popmax 0.0117%, amr).

How common is NMUR2 p.Met239Leu (c.715A>T) in the general population?

NMUR2 p.Met239Leu (c.715A>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about NMUR2 p.Met239Leu (c.715A>T)?

AlphaMissense predicts likely benign (score 0.3131) — an in-silico prediction, not a clinical call.

NMUR2 p.Met239Leu

c.715A>T · VCV4121020

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3131 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3131	likely benign
REVEL	0.182	moderately benign-leaning
SaProt	LLR -9.85	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 4.8	GERP 0.43, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 13 kb · p 0.37 · regional, not allelic
Overall
CADD	24.0	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 0.0117% Admixed American · 7/59,936 alleles

Filtering AF 0.00544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000496% 8/1,611,594 alleles · ultra-rare exomes 8/1,459,368 · genomes 0/152,226 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,562
South Asian	0.0011%	90,858

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.Met239Leu
Coding: c.715A>T
MANE Select: NM_020167
Type: single nucleotide variant
Location: chr5:152404399 (GRCh38)
Gene constraint: LOEUF 1.327 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.92 · 3 PDB
Residue 239: 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-met239leu (accessed [today's date]).

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