Is KRIT1 p.Phe97fs (c.288dup) pathogenic?

KRIT1 p.Phe97fs (c.288dup) is classified Likely pathogenic in KRIT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-22). Very rare (popmax 0.000171%, nfe); Associated with KRIT1-related disorder.

What condition is associated with KRIT1 p.Phe97fs (c.288dup)?

KRIT1 p.Phe97fs (c.288dup) is associated with KRIT1-related disorder (ClinVar).

How common is KRIT1 p.Phe97fs (c.288dup) in the general population?

KRIT1 p.Phe97fs (c.288dup) is very rare (popmax 0.000171%, nfe) (gnomAD).

KRIT1 p.Phe97fs

c.288dup · VCV4896670

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000171%, nfe)

Conditions

KRIT1-related disorder

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 6 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 3.3, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000171% European (non-Finnish) · 2/1,169,654 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000125% 2/1,602,298 alleles · very rare exomes 2/1,450,054 · genomes 0/152,244 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: KRIT1
Protein: p.Phe97fs
Coding: c.288dup
MANE Select: NM_194454
Type: Duplication
Location: chr7:92237733 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 83.01 · 15 PDB
Residue 97: a UniProt-annotated variant site (in ccm1); a β-strand; the 'n-terminal domain similar to nudix hydrolase domain' region

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

Disease context

KRIT1-related disorder

Similar variants

KRIT1 p.Asn663fs Likely pathogenic ★ same condition
KRIT1 p.Leu177fs Likely pathogenic ★ same condition
KRIT1 p.Thr462fs Likely pathogenic ★ same condition
KRIT1 p.Thr693fs Likely pathogenic ★ same condition
KRIT1 p.Val278fs Pathogenic ★ same condition
KRIT1 p.Thr188fs Pathogenic same condition
KRIT1 c.1147-13C>G Pathogenic ★★ same condition
KRIT1 c.1147-2A>G 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-phe97fs (accessed [today's date]).

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