Is NMT2 p.Asp93Val (c.278A>T) pathogenic?

NMT2 p.Asp93Val (c.278A>T) is classified Uncertain significance in NMT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-10). AlphaMissense: ambiguous (0.4821); Ultra-rare (popmax 0.0233%, amr).

How common is NMT2 p.Asp93Val (c.278A>T) in the general population?

NMT2 p.Asp93Val (c.278A>T) is ultra-rare (popmax 0.0233%, amr) (gnomAD).

What do computational predictors say about NMT2 p.Asp93Val (c.278A>T)?

AlphaMissense predicts ambiguous (score 0.4821) — an in-silico prediction, not a clinical call.

NMT2 p.Asp93Val

c.278A>T · VCV3406382

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4821 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4821	ambiguous
REVEL	0.251	benign-leaning
SaProt	LLR -9.22	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 0.79, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 59 kb · p 7.5e-07 · regional, not allelic
Overall
CADD	26.2	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 0.0233% Admixed American · 14/60,002 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.00372% 60/1,614,080 alleles · ultra-rare exomes 58/1,461,874 · genomes 2/152,206 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0233%	4,286
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.008%	12,497
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
European (non-Finnish)	0.00322%	31,053
African / African-American	0.00133%	74,926

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.Asp93Val
Coding: c.278A>T
MANE Select: NM_004808
Type: single nucleotide variant
Location: chr10:15135387 (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-asp93val (accessed [today's date]).

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