Is KIF7 p.Arg53Pro (c.158G>C) pathogenic?

KIF7 p.Arg53Pro (c.158G>C) is classified Uncertain significance in KIF7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-13). AlphaMissense: likely pathogenic (0.8867); Very rare (popmax 6.44e-05%); Associated with Inborn genetic diseases.

What condition is associated with KIF7 p.Arg53Pro (c.158G>C)?

KIF7 p.Arg53Pro (c.158G>C) is associated with Inborn genetic diseases (ClinVar).

How common is KIF7 p.Arg53Pro (c.158G>C) in the general population?

KIF7 p.Arg53Pro (c.158G>C) is very rare (popmax 6.44e-05%) (gnomAD).

What do computational predictors say about KIF7 p.Arg53Pro (c.158G>C)?

AlphaMissense predicts likely pathogenic (score 0.8867) — an in-silico prediction, not a clinical call.

KIF7 p.Arg53Pro

c.158G>C · rs746547718 · VCV2334644

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8867 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.44e-05%)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8867	likely pathogenic · top 10% in KIF7
REVEL	0.78	moderately pathogenic-leaning
SaProt	LLR -16.16	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 0.28, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 25 kb · p 0.00011 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.44e-05%

Overall 6.44e-05% 1/1,551,606 alleles · very rare exomes 1/1,399,222 · genomes 0/152,384 · joint denominator

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.Arg53Pro
Coding: c.158G>C
MANE Select: NM_198525
dbSNP: rs746547718
Type: single nucleotide variant
Location: chr15:89652773 (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 53: the kinesin motor domain; a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KIF7 p.Arg53Leu Uncertain significance ★ same residue
KIF7 p.Arg53Ter Pathogenic ★★ same residue
KIF7 p.Arg53Gly Uncertain significance ★ ⚠ same residue
KIF7 c.328+2T>G Pathogenic/Likely pathogenic ★★ same condition
KIF7 p.Glu844Ter Pathogenic ★★ same condition
KIF7 p.Ala1258Asp Uncertain significance ★★ ⚠ same condition
KIF7 p.Ala1271Thr Uncertain significance ★★ ⚠ same condition
KIF7 p.Ala343Thr Uncertain significance ★★ ⚠ 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-arg53pro (accessed [today's date]).

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