Is NMT2 p.Ser102Pro (c.304T>C) pathogenic?

NMT2 p.Ser102Pro (c.304T>C) is classified Uncertain significance in NMT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: ambiguous (0.5386); Very rare (popmax 8.47e-05%, nfe).

How common is NMT2 p.Ser102Pro (c.304T>C) in the general population?

NMT2 p.Ser102Pro (c.304T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about NMT2 p.Ser102Pro (c.304T>C)?

AlphaMissense predicts ambiguous (score 0.5386) — an in-silico prediction, not a clinical call.

NMT2 p.Ser102Pro

c.304T>C · VCV4120992

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5386 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5386	ambiguous
REVEL	0.253	benign-leaning
SaProt	LLR -8.96	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 59 kb · p 7.5e-07 · regional, not allelic
Overall
CADD	27.0	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 8.47e-05% European (non-Finnish) · 1/1,180,020 alleles

Overall 6.2e-05% 1/1,614,022 alleles · very rare exomes 0/1,461,870 · genomes 1/152,152 · joint denominator

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.Ser102Pro
Coding: c.304T>C
MANE Select: NM_004808
Type: single nucleotide variant
Location: chr10:15135361 (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-ser102pro (accessed [today's date]).

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