Is SETD2 p.Asp1616Val (c.4847A>T) pathogenic?

SETD2 p.Asp1616Val (c.4847A>T) is classified Likely pathogenic in SETD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-03-31). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1.

How common is SETD2 p.Asp1616Val (c.4847A>T) in the general population?

SETD2 p.Asp1616Val (c.4847A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SETD2 p.Asp1616Val (c.4847A>T)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

SETD2 p.Asp1616Val

c.4847A>T · rs1064794751 · VCV420862

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic ✓ concordant with ClinVar · top 1% in SETD2
REVEL	0.923	moderately pathogenic-leaning
SaProt	LLR -15.35	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.26	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.28	constrained · MANE · 19 kb · p 4.3e-27 · regional, not allelic
Overall
CADD	26.5	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: SETD2
Protein: p.Asp1616Val
Coding: c.4847A>T
MANE Select: NM_014159
dbSNP: rs1064794751
Type: single nucleotide variant
Location: chr3:47103416 (GRCh38)
Gene constraint: LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.81 · 43 PDB
Residue 1616: 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; a β-strand

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

Similar variants

SETD2 p.Arg1598Ter Pathogenic/Likely pathogenic ★★ same type
SETD2 p.Arg1740Gln Pathogenic ★★ ⚠ same type
SETD2 p.Arg1740Trp Pathogenic/Likely pathogenic ★★ same type
SETD2 p.Arg441Ter Likely pathogenic ★★ same type
SETD2 p.Glu1718Lys Likely pathogenic ★★ ⚠ same type
SETD2 c.4715+5G>A Uncertain significance ★★ same type
SETD2 p.Ala1121Thr Uncertain significance ★★ ⚠ same type
SETD2 p.Ala679Val 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/setd2-p-asp1616val (accessed [today's date]).

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