Is KIF7 p.Pro42= (c.126A>T) pathogenic?

KIF7 p.Pro42= (c.126A>T) is classified Likely benign in KIF7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-30). Ultra-rare (popmax 0.0334%, mid); Associated with acrocallosal syndrome.

What condition is associated with KIF7 p.Pro42= (c.126A>T)?

KIF7 p.Pro42= (c.126A>T) is associated with acrocallosal syndrome (ClinVar).

How common is KIF7 p.Pro42= (c.126A>T) in the general population?

KIF7 p.Pro42= (c.126A>T) is ultra-rare (popmax 0.0334%, mid) (gnomAD).

KIF7 p.Pro42=

c.126A>T · rs749628860 · VCV1931346

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, mid)

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 -14	GERP -4.7
Overall
CADD	0.258	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0334% Middle Eastern · 2/5,980 alleles

Filtering AF 0.00589% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00245%

Overall 0.000193% 3/1,551,024 alleles · ultra-rare exomes 2/1,398,780 · genomes 1/152,244 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0334%	2,990
Remaining individualsnot grpmax-eligible	0.00166%	60,088

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.Pro42=
Coding: c.126A>T
MANE Select: NM_198525
dbSNP: rs749628860
Type: single nucleotide variant
Location: chr15:89652805 (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 42: the kinesin motor domain; an α-helix

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.Pro42Ala 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-pro42 (accessed [today's date]).

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