Is KIF7 p.Pro430= (c.1290C>T) pathogenic?

KIF7 p.Pro430= (c.1290C>T) is classified Conflicting classifications of pathogenicity in KIF7 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-08). Very rare (popmax 0.00604%, nfe); Associated with acrocallosal syndrome.

What condition is associated with KIF7 p.Pro430= (c.1290C>T)?

KIF7 p.Pro430= (c.1290C>T) is associated with acrocallosal syndrome (ClinVar).

How common is KIF7 p.Pro430= (c.1290C>T) in the general population?

KIF7 p.Pro430= (c.1290C>T) is very rare (popmax 0.00604%, nfe) (gnomAD).

KIF7 p.Pro430=

c.1290C>T · rs886051534 · VCV317368

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00604%, nfe)

Conditions

acrocallosal 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 -4.9	GERP -2.2
Overall
CADD	0.886	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00604% European (non-Finnish) · 56/927,456 alleles

Filtering AF 0.00477% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00428%

Overall 0.00536% 61/1,137,564 alleles · very rare exomes 53/989,242 · genomes 8/148,322 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00604%	16,562
Remaining individualsnot grpmax-eligible	0.00518%	19,311
African / African-American	0.005%	20,003

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: KIF7
Protein: p.Pro430=
Coding: c.1290C>T
MANE Select: NM_198525
dbSNP: rs886051534
Type: single nucleotide variant
Location: chr15:89648408 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.07 · 5 PDB
Residue 430: the 'interaction with smo' region; the 'interaction with dlg5' region

Full KIF7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Similar variants

KIF7 p.Pro430Ser Uncertain significance ★ ⚠ same residue
KIF7 c.1443+2T>C Likely pathogenic ★★ same condition
KIF7 c.1561-1G>A Likely pathogenic ★★ same condition
KIF7 c.1789-2A>G Likely pathogenic ★★ same condition
KIF7 c.2593-3C>G Pathogenic ★★ same condition
KIF7 c.328+2T>G Pathogenic/Likely pathogenic ★★ same condition
KIF7 c.3518-1G>C Likely pathogenic ★★ same condition
KIF7 c.923+2T>G 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/kif7-p-pro430 (accessed [today's date]).

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