Is NSD1 p.Ala79= (c.237C>T) pathogenic?

NSD1 p.Ala79= (c.237C>T) is classified Likely benign in NSD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-23). Very rare (popmax 6.2e-05%).

How common is NSD1 p.Ala79= (c.237C>T) in the general population?

NSD1 p.Ala79= (c.237C>T) is very rare (popmax 6.2e-05%) (gnomAD).

NSD1 p.Ala79=

c.237C>T · VCV3621021

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Overall
CADD	14.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,611,812 alleles · very rare exomes 1/1,459,584 · genomes 0/152,228 · 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: NSD1
Protein: p.Ala79=
Coding: c.237C>T
MANE Select: NM_022455
Type: single nucleotide variant
Location: chr5:177135340 (GRCh38)
Gene constraint: LOEUF 0.144 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 45.26 · 4 PDB

Full NSD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NSD1 p.Ala79Thr Uncertain significance ★ ⚠ same residue
NSD1 p.Ala79Val Uncertain significance ★ ⚠ same residue
NSD1 c.1064-2A>G Pathogenic/Likely pathogenic ★★ same type
NSD1 c.3921+1G>A Likely pathogenic ★★ same type
NSD1 c.4192+2T>G Pathogenic ★★ same type
NSD1 c.4303-1G>C Likely pathogenic ★★ same type
NSD1 c.4378+1G>A Pathogenic/Likely pathogenic ★★ same type
NSD1 c.4766-2A>G Pathogenic/Likely pathogenic ★★ 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/nsd1-p-ala79 (accessed [today's date]).

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