Is GEN1 p.Lys883= (c.2649A>G) pathogenic?

GEN1 p.Lys883= (c.2649A>G) is classified Likely benign in GEN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-13). Absent from gnomAD v4.1.

How common is GEN1 p.Lys883= (c.2649A>G) in the general population?

GEN1 p.Lys883= (c.2649A>G) is absent from gnomAD v4.1 (gnomAD).

GEN1 p.Lys883=

c.2649A>G · rs1672857983 · VCV2981308

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.75	GERP -2.9, phastCons 0.78
Overall
CADD	2.175	PHRED · no single calibrated threshold — expert panels disagree

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: GEN1
Protein: p.Lys883=
Coding: c.2649A>G
MANE Select: NM_001130009
dbSNP: rs1672857983
Type: single nucleotide variant
Location: chr2:17781861 (GRCh38)
Gene constraint: LOEUF 1.422 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
Structure: AlphaFold pLDDT 61.79 · 1 PDB

Full GEN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GEN1 p.Lys883Asn Uncertain significance ★★ ⚠ same residue
GEN1 c.1264+1G>T Uncertain significance ★★ same type
GEN1 c.953+4A>G Uncertain significance ★★ same type
GEN1 p.Ala135Ser Uncertain significance ★★ ⚠ same type
GEN1 p.Ala197Thr Uncertain significance ★★ ⚠ same type
GEN1 p.Ala320Pro Uncertain significance ★★ ⚠ same type
GEN1 p.Ala447Val Uncertain significance ★★ ⚠ same type
GEN1 p.Ala448Thr 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/gen1-p-lys883 (accessed [today's date]).

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