Is NNMT p.Val82Phe (c.244G>T) pathogenic?

NNMT p.Val82Phe (c.244G>T) is classified Uncertain significance in NNMT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely benign (0.1833); Ultra-rare (popmax 0.0165%, mid).

How common is NNMT p.Val82Phe (c.244G>T) in the general population?

NNMT p.Val82Phe (c.244G>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about NNMT p.Val82Phe (c.244G>T)?

AlphaMissense predicts likely benign (score 0.1833) — an in-silico prediction, not a clinical call.

NNMT p.Val82Phe

c.244G>T · VCV4558308

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1833 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1833	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -8.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.87	GERP -3.8
Regional constraint	o/e 1.19	unconstrained · MANE · 16 kb · p 0.00057 · regional, not allelic
Overall
CADD	14.69	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0165% Middle Eastern · 1/6,048 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000186% 3/1,614,062 alleles · ultra-rare exomes 3/1,461,868 · genomes 0/152,194 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,048
Admixed American	0.00333%	30,007

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: NNMT
Protein: p.Val82Phe
Coding: c.244G>T
MANE Select: NM_006169
Type: single nucleotide variant
Location: chr11:114298040 (GRCh38)
Gene constraint: LOEUF 1.306 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.11 · 33 PDB
Residue 82: a β-strand

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

Similar variants

NNMT p.Ala169Thr Uncertain significance ★ ⚠ same type
NNMT p.Ala179Ser Uncertain significance ★ ⚠ same type
NNMT p.Ala179Val Uncertain significance ★ ⚠ same type
NNMT p.Ala198Thr Uncertain significance ★ ⚠ same type
NNMT p.Ala257Val Uncertain significance ★ ⚠ same type
NNMT p.Arg18Gln Uncertain significance ★ ⚠ same type
NNMT p.Arg18Trp Uncertain significance ★ ⚠ same type
NNMT p.Arg218Gln 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/nnmt-p-val82phe (accessed [today's date]).

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