Is NMT2 p.Val183Ile (c.547G>A) pathogenic?

NMT2 p.Val183Ile (c.547G>A) is classified Uncertain significance in NMT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-09). AlphaMissense: ambiguous (0.4914); Ultra-rare (popmax 0.0107%, afr).

How common is NMT2 p.Val183Ile (c.547G>A) in the general population?

NMT2 p.Val183Ile (c.547G>A) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about NMT2 p.Val183Ile (c.547G>A)?

AlphaMissense predicts ambiguous (score 0.4914) — an in-silico prediction, not a clinical call.

NMT2 p.Val183Ile

c.547G>A · VCV3300173

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4914 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Computational evidence

Protein change
AlphaMissense	0.4914	ambiguous
REVEL	0.401	indeterminate
SaProt	LLR -5.10	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 59 kb · p 7.5e-07 · regional, not allelic
Overall
CADD	24.4	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 0.0107% African / African-American · 8/75,050 alleles

Filtering AF 0.00639% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00592%

Overall 0.00651% 105/1,614,074 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,381
European (non-Finnish)	0.00771%	12,966
Remaining individualsnot grpmax-eligible	0.0048%	20,834
Finnishnot grpmax-eligible	0.00312%	32,018
Admixed American	0.00167%	60,030

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: NMT2
Protein: p.Val183Ile
Coding: c.547G>A
MANE Select: NM_004808
Type: single nucleotide variant
Location: chr10:15133108 (GRCh38)
Gene constraint: LOEUF 0.737 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.81 · 3 PDB

Full NMT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NMT2 p.Ala103Thr Uncertain significance ★ ⚠ same type
NMT2 p.Ala139Thr Uncertain significance ★ ⚠ same type
NMT2 p.Ala233Thr Uncertain significance ★ same type
NMT2 p.Ala262Pro Uncertain significance ★ ⚠ same type
NMT2 p.Ala285Thr Uncertain significance ★ ⚠ same type
NMT2 p.Ala285Val Uncertain significance ★ ⚠ same type
NMT2 p.Ala420Thr Uncertain significance ★ ⚠ same type
NMT2 p.Ala440Val 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/nmt2-p-val183ile (accessed [today's date]).

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