Is NSD2 p.Val951Phe (c.2851G>T) pathogenic?

NSD2 p.Val951Phe (c.2851G>T) is classified Likely benign in NSD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). AlphaMissense: likely benign (0.1187); Very rare (popmax 0.00017%, nfe).

How common is NSD2 p.Val951Phe (c.2851G>T) in the general population?

NSD2 p.Val951Phe (c.2851G>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about NSD2 p.Val951Phe (c.2851G>T)?

AlphaMissense predicts likely benign (score 0.1187) — an in-silico prediction, not a clinical call.

NSD2 p.Val951Phe

c.2851G>T · rs1724781986 · VCV2090945

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1187 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1187	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -8.16	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 3.6	GERP 0.69, phastCons 1
Regional constraint	o/e 0.29	constrained · MANE · 20 kb · p 9e-56 · regional, not allelic
Overall
CADD	18.97	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 0.00017% European (non-Finnish) · 2/1,179,590 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,350 alleles · very rare exomes 2/1,461,032 · genomes 0/152,318 · 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: NSD2
Protein: p.Val951Phe
Coding: c.2851G>T
MANE Select: NM_001042424
dbSNP: rs1724781986
Type: single nucleotide variant
Location: chr4:1956158 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.22 · 24 PDB
Residue 951: a UniProt-annotated variant site (in raust)

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-val951phe (accessed [today's date]).

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