Is NSD2 p.Arg319Ser (c.957G>T) pathogenic?

NSD2 p.Arg319Ser (c.957G>T) is classified Likely pathogenic in NSD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-30). AlphaMissense: likely pathogenic (0.709); Absent from gnomAD v4.1; Associated with NSD2-related disorder.

What condition is associated with NSD2 p.Arg319Ser (c.957G>T)?

NSD2 p.Arg319Ser (c.957G>T) is associated with NSD2-related disorder (ClinVar).

How common is NSD2 p.Arg319Ser (c.957G>T) in the general population?

NSD2 p.Arg319Ser (c.957G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NSD2 p.Arg319Ser (c.957G>T)?

AlphaMissense predicts likely pathogenic (score 0.709) — an in-silico prediction, not a clinical call.

NSD2 p.Arg319Ser

c.957G>T · rs1577434780 · VCV638610

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.709 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

NSD2-related disorder

Computational evidence

Protein change
AlphaMissense	0.709	likely pathogenic ✓ concordant with ClinVar
REVEL	0.467	indeterminate
SaProt	LLR -10.31	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.66	GERP -3.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 34 kb · p 0.024 · regional, not allelic
Overall
CADD	22.1	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.Arg319Ser
Coding: c.957G>T
MANE Select: NM_001042424
dbSNP: rs1577434780
Type: single nucleotide variant
Location: chr4:1918170 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.22 · 24 PDB
Residue 319: an α-helix

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

Disease context

NSD2-related disorder

Similar variants

NSD2 p.Gly92Ser Uncertain significance ★★ ⚠ same condition
NSD2 c.761-1G>C Likely pathogenic ★ same condition
NSD2 p.Arg944Trp Likely pathogenic ★ same condition
NSD2 p.Cys743Phe Likely pathogenic ★ same condition
NSD2 p.Cys813Tyr Likely pathogenic ★ same condition
NSD2 p.Glu123Ter Pathogenic ★ same condition
NSD2 p.Val1093Ala Likely pathogenic ★ same condition
NSD2 p.Gly840Val Uncertain significance ★ ⚠ same condition

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-arg319ser (accessed [today's date]).

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