Is SETD2 p.Ser1572= (c.4716G>A) pathogenic?

SETD2 p.Ser1572= (c.4716G>A) is classified Likely benign in SETD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-19). Very rare (popmax 0.00883%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SETD2 p.Ser1572= (c.4716G>A)?

SETD2 p.Ser1572= (c.4716G>A) is associated with Inborn genetic diseases (ClinVar).

How common is SETD2 p.Ser1572= (c.4716G>A) in the general population?

SETD2 p.Ser1572= (c.4716G>A) is very rare (popmax 0.00883%, nfe) (gnomAD).

SETD2 p.Ser1572=

c.4716G>A · VCV3794630

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00883%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -1.5, phastCons 1
Overall
CADD	12.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00883% European (non-Finnish) · 104/1,177,148 alleles

Filtering AF 0.00743% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00694%

Overall 0.00652% 105/1,609,450 alleles · very rare exomes 105/1,457,404 · genomes 0/152,046 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00883%	11,319
Remaining individualsnot grpmax-eligible	0.00161%	62,268

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: SETD2
Protein: p.Ser1572=
Coding: c.4716G>A
MANE Select: NM_014159
Type: single nucleotide variant
Location: chr3:47106120 (GRCh38)
Gene constraint: LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.81 · 43 PDB
Residue 1572: a UniProt-annotated variant site (in aml; uncertain significance; somatic mutation); a UniProt-annotated variant site (in all; uncertain significance; somatic mutation); the 'interaction with tuba1a' region; the set domain

Full SETD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SETD2 p.Ser1572Leu Likely benign ★ same residue
SETD2 c.4715+5G>A Uncertain significance ★★ same condition
SETD2 p.Arg1197Thr Uncertain significance ★★ ⚠ same condition
SETD2 p.Arg368Gln Uncertain significance ★★ ⚠ same condition
SETD2 p.Arg540Gln Uncertain significance ★★ ⚠ same condition
SETD2 p.Asn1303Ser Uncertain significance ★★ ⚠ same condition
SETD2 p.Asn840Ser Uncertain significance ★★ ⚠ same condition
SETD2 p.Asp1169Gly 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/setd2-p-ser1572 (accessed [today's date]).

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