Is NMUR1 p.Val323Met (c.967G>A) pathogenic?

NMUR1 p.Val323Met (c.967G>A) is classified Uncertain significance in NMUR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely benign (0.1928); Very rare (popmax 0.00934%, afr).

How common is NMUR1 p.Val323Met (c.967G>A) in the general population?

NMUR1 p.Val323Met (c.967G>A) is very rare (popmax 0.00934%, afr) (gnomAD).

What do computational predictors say about NMUR1 p.Val323Met (c.967G>A)?

AlphaMissense predicts likely benign (score 0.1928) — an in-silico prediction, not a clinical call.

NMUR1 p.Val323Met

c.967G>A · VCV4121008

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1928 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1928	likely benign
REVEL	0.288	benign-leaning
SaProt	LLR -10.89	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.046	GERP -0.67, phastCons 0.001
Regional constraint	o/e 0.91	unconstrained · MANE · 5,315 bp · p 0.033 · regional, not allelic
Overall
CADD	17.22	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 0.00934% African / African-American · 7/74,918 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00254% 41/1,613,974 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00934%	10,703
European (non-Finnish)	0.0028%	35,758
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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: NMUR1
Protein: p.Val323Met
Coding: c.967G>A
MANE Select: NM_006056
Type: single nucleotide variant
Location: chr2:231525357 (GRCh38)
Gene constraint: LOEUF 1.399 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.23 · 2 PDB

Full NMUR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NMUR1 p.Arg259Trp Benign/Likely benign ★★ same type
NMUR1 p.Ala176Val Uncertain significance ★ ⚠ same type
NMUR1 p.Ala236Val Uncertain significance ★ ⚠ same type
NMUR1 p.Ala25Thr Uncertain significance ★ ⚠ same type
NMUR1 p.Ala269Val Uncertain significance ★ ⚠ same type
NMUR1 p.Ala350Val Uncertain significance ★ ⚠ same type
NMUR1 p.Ala412Ser Uncertain significance ★ ⚠ same type
NMUR1 p.Arg159His 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/nmur1-p-val323met (accessed [today's date]).

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