Is KRIT1 p.Phe234fs (c.700_703del) pathogenic?

KRIT1 p.Phe234fs (c.700703del) is classified Pathogenic in KRIT1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-23). Associated with cerebral cavernous malformation.

What condition is associated with KRIT1 p.Phe234fs (c.700_703del)?

KRIT1 p.Phe234fs (c.700_703del) is associated with cerebral cavernous malformation (ClinVar).

KRIT1 p.Phe234fs

c.700_703del · VCV3381025

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 8 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 3.4, phastCons 1

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

Variant & gene context

Gene: KRIT1
Protein: p.Phe234fs
Coding: c.700_703del
MANE Select: NM_194454
Type: Microsatellite
Location: chr7:92235429 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 83.01 · 15 PDB
Residue 234: 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 c.1255-1_1256del Pathogenic ★★ same condition
KRIT1 c.1730+4_1730+7del Pathogenic/Likely pathogenic ★★ same condition
KRIT1 p.Asn402fs Pathogenic/Likely pathogenic ★★ same condition
KRIT1 p.Gln401fs Pathogenic ★★ same condition
KRIT1 p.Gln455fs Pathogenic ★★ same condition
KRIT1 p.Gln573fs Pathogenic/Likely pathogenic ★★ same condition
KRIT1 p.Glu567_Ser568insTer Pathogenic ★★ same condition
KRIT1 p.His326fs Pathogenic/Likely 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-phe234fs (accessed [today's date]).

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