Is NMT2 p.Ala285Val (c.854C>T) pathogenic?

NMT2 p.Ala285Val (c.854C>T) is classified Uncertain significance in NMT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely pathogenic (0.927); Ultra-rare (popmax 0.0104%, amr).

How common is NMT2 p.Ala285Val (c.854C>T) in the general population?

NMT2 p.Ala285Val (c.854C>T) is ultra-rare (popmax 0.0104%, amr) (gnomAD).

What do computational predictors say about NMT2 p.Ala285Val (c.854C>T)?

AlphaMissense predicts likely pathogenic (score 0.927) — an in-silico prediction, not a clinical call.

NMT2 p.Ala285Val

c.854C>T · rs535699588 · VCV3200855

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.927 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0104%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.927	likely pathogenic
REVEL	0.51	indeterminate
SaProt	LLR -12.91	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 59 kb · p 7.5e-07 · regional, not allelic
Overall
CADD	23.9	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

Grpmax group 0.0104% Admixed American · 6/57,922 alleles

Filtering AF 0.00441% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00304%

Overall 0.00138% 22/1,590,568 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0104%	9,654
African / African-American	0.00404%	24,767
South Asian	0.00116%	86,072
European (non-Finnish)	0.00103%	97,257

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.Ala285Val
Coding: c.854C>T
MANE Select: NM_004808
dbSNP: rs535699588
Type: single nucleotide variant
Location: chr10:15130178 (GRCh38)
Gene constraint: LOEUF 0.737 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.81 · 3 PDB
Residue 285: a β-strand

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

Similar variants

NMT2 p.Ala285Thr Uncertain significance ★ ⚠ same residue
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.Ala420Thr Uncertain significance ★ ⚠ same type
NMT2 p.Ala440Val Uncertain significance ★ ⚠ same type
NMT2 p.Arg148Cys 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-ala285val (accessed [today's date]).

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