Is KIZ p.Phe94= (c.282C>T) pathogenic?

KIZ p.Phe94= (c.282C>T) is classified Likely benign in KIZ (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-03-16). Very rare (popmax 8.55e-05%, nfe); Associated with KIZ-related disorder.

What condition is associated with KIZ p.Phe94= (c.282C>T)?

KIZ p.Phe94= (c.282C>T) is associated with KIZ-related disorder (ClinVar).

How common is KIZ p.Phe94= (c.282C>T) in the general population?

KIZ p.Phe94= (c.282C>T) is very rare (popmax 8.55e-05%, nfe) (gnomAD).

KIZ p.Phe94=

c.282C>T · rs1320517337 · VCV3045609

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.55e-05%, nfe)

Conditions

KIZ-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.27	donor loss · deltas
Constraint at this position
Conservation	phyloP 0.32	GERP -5, phastCons 0.088
Overall
CADD	3.612	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.55e-05% European (non-Finnish) · 1/1,169,718 alleles

Overall 0.000126% 2/1,590,022 alleles · very rare exomes 2/1,437,802 · genomes 0/152,220 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00163%	61,532
European (non-Finnish)grpmax	8.55e-05%	1,169,718

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: KIZ
Protein: p.Phe94=
Coding: c.282C>T
MANE Select: NM_018474
dbSNP: rs1320517337
Type: single nucleotide variant
Location: chr20:21136519 (GRCh38)
Gene constraint: LOEUF 1.227 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.82

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

Disease context

KIZ-related disorder

Similar variants

KIZ c.1447-2A>G Likely pathogenic ★★ same condition
KIZ c.1612+2T>G Likely pathogenic ★★ same condition
KIZ p.Arg195Ter Pathogenic/Likely pathogenic ★★ same condition
KIZ p.Arg76Ter Pathogenic ★★ same condition
KIZ p.Gln199Ter Pathogenic/Likely pathogenic ★★ same condition
KIZ p.Gln22Ter Pathogenic/Likely pathogenic ★★ same condition
KIZ p.Leu625Ter Pathogenic/Likely pathogenic ★★ same condition
KIZ p.Met1Ile 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/kiz-p-phe94 (accessed [today's date]).

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