Is KIFBP p.Val22= (c.66G>A) pathogenic?

KIFBP p.Val22= (c.66G>A) is classified Conflicting classifications of pathogenicity in KIFBP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2019-04-30). Ultra-rare (popmax 0.0164%, mid); Associated with Goldberg-Shprintzen syndrome.

What condition is associated with KIFBP p.Val22= (c.66G>A)?

KIFBP p.Val22= (c.66G>A) is associated with Goldberg-Shprintzen syndrome (ClinVar).

How common is KIFBP p.Val22= (c.66G>A) in the general population?

KIFBP p.Val22= (c.66G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

KIFBP p.Val22=

c.66G>A · rs368452753 · VCV877691

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

Goldberg-Shprintzen syndrome

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 2.8	GERP -1.4, phastCons 1
Overall
CADD	8.204	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000991% 16/1,614,140 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Admixed American	0.00333%	30,009
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.000932%	107,279

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: KIFBP
Protein: p.Val22=
Coding: c.66G>A
MANE Select: NM_015634
dbSNP: rs368452753
Type: single nucleotide variant
Location: chr10:68988898 (GRCh38)
Gene constraint: LOEUF 1.016 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.76 · 6 PDB

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

Disease context

Goldberg-Shprintzen syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KIFBP p.Ser200Ter Pathogenic ★★ same condition
KIFBP p.Ala39Gly Uncertain significance ★★ same condition
KIFBP p.Ala590Thr Uncertain significance ★★ ⚠ same condition
KIFBP p.Arg442Thr Uncertain significance ★★ ⚠ same condition
KIFBP p.Glu240Lys Uncertain significance ★★ ⚠ same condition
KIFBP p.Glu301Lys Uncertain significance ★★ ⚠ same condition
KIFBP p.Ile261Val Uncertain significance ★★ ⚠ same condition
KIFBP p.Val539Ile Uncertain significance ★★ ⚠ 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/kifbp-p-val22 (accessed [today's date]).

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