Is KIF7 p.Phe83Val (c.247T>G) pathogenic?

KIF7 p.Phe83Val (c.247T>G) is classified Uncertain significance in KIF7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-06-10). AlphaMissense: ambiguous (0.4655); Very rare (popmax 0.00392%, amr); Associated with acrocallosal syndrome.

What condition is associated with KIF7 p.Phe83Val (c.247T>G)?

KIF7 p.Phe83Val (c.247T>G) is associated with acrocallosal syndrome, multiple epiphyseal dysplasia, Al-Gazali type, hydrolethalus syndrome 2 (ClinVar).

How common is KIF7 p.Phe83Val (c.247T>G) in the general population?

KIF7 p.Phe83Val (c.247T>G) is very rare (popmax 0.00392%, amr) (gnomAD).

What do computational predictors say about KIF7 p.Phe83Val (c.247T>G)?

AlphaMissense predicts ambiguous (score 0.4655) — an in-silico prediction, not a clinical call.

KIF7 p.Phe83Val

c.247T>G · rs770614646 · VCV1306754

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4655 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00392%, amr)

Conditions

acrocallosal syndrome

Computational evidence

Protein change
AlphaMissense	0.4655	ambiguous
REVEL	0.6	indeterminate
SaProt	LLR -6.76	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP -4.9, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 25 kb · p 0.00011 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00392% Admixed American · 2/50,986 alleles

Filtering AF 0.00134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00112%

Overall 0.00174% 27/1,551,268 alleles · very rare exomes 26/1,399,038 · genomes 1/152,230 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00392%	25,493
South Asian	0.00238%	42,016
European (non-Finnish)	0.00201%	49,853

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.Phe83Val
Coding: c.247T>G
MANE Select: NM_198525
dbSNP: rs770614646
Type: single nucleotide variant
Location: chr15:89652684 (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 83: 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

Also linked: multiple epiphyseal dysplasia, Al-Gazali type hydrolethalus syndrome 2

Similar variants

KIF7 p.Phe83Leu Uncertain significance ★★ ⚠ same residue
KIF7 p.Phe83= Likely benign ★ 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-phe83val (accessed [today's date]).

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