Is KRIT1 p.Ser583fs (c.1742dup) pathogenic?

KRIT1 p.Ser583fs (c.1742dup) is classified Pathogenic in KRIT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-27). No gnomAD frequency available for this variant; Associated with cerebral cavernous malformation.

What condition is associated with KRIT1 p.Ser583fs (c.1742dup)?

KRIT1 p.Ser583fs (c.1742dup) is associated with cerebral cavernous malformation (ClinVar).

How common is KRIT1 p.Ser583fs (c.1742dup) in the general population?

KRIT1 p.Ser583fs (c.1742dup) is no gnomAD frequency available for this variant (gnomAD).

KRIT1 p.Ser583fs

c.1742dup · rs2535716449 · VCV2017538

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

cerebral cavernous malformation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 16 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.97	GERP -3.1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: KRIT1
Protein: p.Ser583fs
Coding: c.1742dup
MANE Select: NM_194454
dbSNP: rs2535716449
Type: Duplication
Location: chr7:92213967 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 83.01 · 15 PDB
Residue 583: the ferm domain; a turn

Full KRIT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cerebral cavernous malformation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KRIT1 p.Ile584fs Pathogenic ★★ same condition
KRIT1 p.Ser313fs Pathogenic ★★ same condition
KRIT1 p.Tyr133fs Pathogenic ★★ same condition
KRIT1 c.730-16dup Likely benign ★★ same condition
KRIT1 c.846-5dup Benign/Likely benign ★★ same condition
KRIT1 p.Arg49fs Pathogenic ★ same condition
KRIT1 p.Arg623fs Pathogenic ★ same condition
KRIT1 p.Asn599fs Pathogenic ★ 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/krit1-p-ser583fs (accessed [today's date]).

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