Is PNMT p.Ser71Ala (c.211T>G) pathogenic?

PNMT p.Ser71Ala (c.211T>G) is classified Uncertain significance in PNMT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-30). AlphaMissense: likely benign (0.0726); Absent from gnomAD v4.1.

How common is PNMT p.Ser71Ala (c.211T>G) in the general population?

PNMT p.Ser71Ala (c.211T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PNMT p.Ser71Ala (c.211T>G)?

AlphaMissense predicts likely benign (score 0.0726) — an in-silico prediction, not a clinical call.

PNMT p.Ser71Ala

c.211T>G · rs1597807869 · VCV2552651

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0726 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0726	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -7.06	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.1	GERP -1.5, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,910 bp · p 0.65 · regional, not allelic
Overall
CADD	13.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PNMT
Protein: p.Ser71Ala
Coding: c.211T>G
MANE Select: NM_002686
dbSNP: rs1597807869
Type: single nucleotide variant
Location: chr17:39669637 (GRCh38)
Gene constraint: LOEUF 1.458 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.64 · 44 PDB

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

Similar variants

PNMT p.Ala41= Benign ★★ same type
PNMT p.Ala21Glu Uncertain significance ★ ⚠ same type
PNMT p.Ala227Thr Uncertain significance ★ ⚠ same type
PNMT p.Ala24Ser Uncertain significance ★ ⚠ same type
PNMT p.Ala26Pro Uncertain significance ★ ⚠ same type
PNMT p.Ala41Val Uncertain significance ★ ⚠ same type
PNMT p.Ala66Pro Uncertain significance ★ ⚠ same type
PNMT p.Arg107His 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/pnmt-p-ser71ala (accessed [today's date]).

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