Is SETD5 p.Lys698Arg (c.2093A>G) pathogenic?

SETD5 p.Lys698Arg (c.2093A>G) is classified Uncertain significance in SETD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-20). AlphaMissense: likely benign (0.3172); Absent from gnomAD v4.1.

How common is SETD5 p.Lys698Arg (c.2093A>G) in the general population?

SETD5 p.Lys698Arg (c.2093A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SETD5 p.Lys698Arg (c.2093A>G)?

AlphaMissense predicts likely benign (score 0.3172) — an in-silico prediction, not a clinical call.

SETD5 p.Lys698Arg

c.2093A>G · VCV3381518

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3172 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3172	likely benign
REVEL	0.824	moderately pathogenic-leaning
SaProt	LLR -6.05	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 26 kb · p 0.85 · regional, not allelic
Overall
CADD	25.6	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: SETD5
Protein: p.Lys698Arg
Coding: c.2093A>G
MANE Select: NM_001080517
Type: single nucleotide variant
Location: chr3:9447996 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 47.10
Residue 698: a UniProt-annotated variant site (in mrd23)

Full SETD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SETD5 c.1441-1G>A Pathogenic ★★ same type
SETD5 c.1525-1G>C Pathogenic/Likely pathogenic ★★ same type
SETD5 c.2347-1G>A Pathogenic ★★ same type
SETD5 c.2347-7A>G Pathogenic ★★ same type
SETD5 c.3631+1G>A Pathogenic ★★ same type
SETD5 c.960-5C>G Pathogenic/Likely pathogenic ★★ same type
SETD5 p.Arg1001Ter Pathogenic ★★ same type
SETD5 p.Arg1072Ter 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/setd5-p-lys698arg (accessed [today's date]).

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