Is NSD2 p.Pro357Ser (c.1069C>T) pathogenic?

NSD2 p.Pro357Ser (c.1069C>T) is classified Conflicting classifications of pathogenicity in NSD2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-07-30). AlphaMissense: likely benign (0.1468); Absent from gnomAD v4.1.

How common is NSD2 p.Pro357Ser (c.1069C>T) in the general population?

NSD2 p.Pro357Ser (c.1069C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NSD2 p.Pro357Ser (c.1069C>T)?

AlphaMissense predicts likely benign (score 0.1468) — an in-silico prediction, not a clinical call.

NSD2 p.Pro357Ser

c.1069C>T · rs2108804497 · VCV1680164

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1468 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1468	likely benign
REVEL	0.267	benign-leaning
SaProt	LLR -6.70	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 5.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 34 kb · p 0.024 · regional, not allelic
Overall
CADD	24.8	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

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: NSD2
Protein: p.Pro357Ser
Coding: c.1069C>T
MANE Select: NM_001042424
dbSNP: rs2108804497
Type: single nucleotide variant
Location: chr4:1918282 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.22 · 24 PDB
Residue 357: an α-helix

Full NSD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NSD2 p.Arg450Ter Likely pathogenic ★★ same type
NSD2 p.Arg755Ter Pathogenic/Likely pathogenic ★★ same type
NSD2 p.Arg935Ter Pathogenic ★★ same type
NSD2 p.Pro895Leu Pathogenic ★★ same type
NSD2 p.Ala320Thr Uncertain significance ★★ ⚠ same type
NSD2 p.Ala383Gly Uncertain significance ★★ ⚠ same type
NSD2 p.Ala693Asp Uncertain significance ★★ ⚠ same type
NSD2 p.Ala965Thr 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/nsd2-p-pro357ser (accessed [today's date]).

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