Is KIF7 p.Pro433= (c.1299C>A) pathogenic?

KIF7 p.Pro433= (c.1299C>A) is classified Likely benign in KIF7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-14). Rare (popmax 0.108%, afr); Associated with acrocallosal syndrome.

What condition is associated with KIF7 p.Pro433= (c.1299C>A)?

KIF7 p.Pro433= (c.1299C>A) is associated with acrocallosal syndrome (ClinVar).

How common is KIF7 p.Pro433= (c.1299C>A) in the general population?

KIF7 p.Pro433= (c.1299C>A) is rare (popmax 0.108%, afr) (gnomAD).

KIF7 p.Pro433=

c.1299C>A · rs921943205 · VCV1122285

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.108%, afr)

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 -11	GERP -2.5
Overall
CADD	0.042	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.108% African / African-American · 65/60,434 alleles

Filtering AF 0.0865% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.079%

Overall 0.00738% 85/1,151,826 alleles · rare exomes 38/1,003,110 · genomes 47/148,716 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.108%	930
Admixed American	0.0148%	6,777
South Asian	0.00702%	14,249
Remaining individualsnot grpmax-eligible	0.00507%	19,726
European (non-Finnish)	0.00139%	72,000

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.Pro433=
Coding: c.1299C>A
MANE Select: NM_198525
dbSNP: rs921943205
Type: single nucleotide variant
Location: chr15:89648399 (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 433: 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.Pro433Thr Uncertain significance ★★ ⚠ same residue
KIF7 p.Pro433Leu 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

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-pro433 (accessed [today's date]).

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