Is NMUR1 p.Thr174Met (c.521C>T) pathogenic?

NMUR1 p.Thr174Met (c.521C>T) is classified Uncertain significance in NMUR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-03). AlphaMissense: likely benign (0.2145); Very rare (popmax 0.00769%, sas).

How common is NMUR1 p.Thr174Met (c.521C>T) in the general population?

NMUR1 p.Thr174Met (c.521C>T) is very rare (popmax 0.00769%, sas) (gnomAD).

What do computational predictors say about NMUR1 p.Thr174Met (c.521C>T)?

AlphaMissense predicts likely benign (score 0.2145) — an in-silico prediction, not a clinical call.

NMUR1 p.Thr174Met

c.521C>T · VCV3406392

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2145 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2145	likely benign
REVEL	0.678	pathogenic-leaning
SaProt	LLR -13.87	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP 2.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 5,315 bp · p 0.033 · regional, not allelic
Overall
CADD	24.6	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 0.00769% South Asian · 7/91,082 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00118% 19/1,613,632 alleles · very rare exomes 18/1,461,384 · genomes 1/152,248 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,012
Admixed American	0.00167%	60,006
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.000847%	118,004

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.Thr174Met
Coding: c.521C>T
MANE Select: NM_006056
Type: single nucleotide variant
Location: chr2:231528500 (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-thr174met (accessed [today's date]).

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