Is KIF7 p.Pro24= (c.72A>C) pathogenic?

KIF7 p.Pro24= (c.72A>C) is classified Conflicting classifications of pathogenicity in KIF7 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-06-12). Ultra-rare (popmax 0.034%, mid); Associated with hydrolethalus syndrome 2.

What condition is associated with KIF7 p.Pro24= (c.72A>C)?

KIF7 p.Pro24= (c.72A>C) is associated with hydrolethalus syndrome 2, acrocallosal syndrome, multiple epiphyseal dysplasia, Al-Gazali type (ClinVar).

How common is KIF7 p.Pro24= (c.72A>C) in the general population?

KIF7 p.Pro24= (c.72A>C) is ultra-rare (popmax 0.034%, mid) (gnomAD).

KIF7 p.Pro24=

c.72A>C · rs773325406 · VCV288230

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.034%, mid)

Conditions

hydrolethalus syndrome 2

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 -8.9	GERP -4.8
Overall
CADD	2.021	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.034% Middle Eastern · 2/5,874 alleles

Filtering AF 0.0215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.00213% 33/1,547,456 alleles · ultra-rare exomes 23/1,395,248 · genomes 10/152,208 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.034%	2,937
African / African-American	0.0315%	3,174
Remaining individualsnot grpmax-eligible	0.0117%	8,564
Admixed American	0.00196%	50,946

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.Pro24=
Coding: c.72A>C
MANE Select: NM_198525
dbSNP: rs773325406
Type: single nucleotide variant
Location: chr15:89652859 (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 24: the kinesin motor domain; an α-helix

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

Disease context

hydrolethalus syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: acrocallosal syndrome multiple epiphyseal dysplasia, Al-Gazali type

Similar variants

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
KIF7 p.Arg1111Ter 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-pro24 (accessed [today's date]).

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