Is KIF7 p.Arg641= (c.1921A>C) pathogenic?

KIF7 p.Arg641= (c.1921A>C) is classified Conflicting classifications of pathogenicity in KIF7 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-06-05). Ultra-rare (popmax 0.0107%, afr); Associated with acrocallosal syndrome.

What condition is associated with KIF7 p.Arg641= (c.1921A>C)?

KIF7 p.Arg641= (c.1921A>C) is associated with acrocallosal syndrome (ClinVar).

How common is KIF7 p.Arg641= (c.1921A>C) in the general population?

KIF7 p.Arg641= (c.1921A>C) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

KIF7 p.Arg641=

c.1921A>C · rs137905815 · VCV1051441

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Conditions

acrocallosal syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2	GERP 0.24, phastCons 1
Overall
CADD	9.972	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0107% African / African-American · 8/75,040 alleles

Filtering AF 0.00527% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00093% 15/1,613,302 alleles · ultra-rare exomes 10/1,461,012 · genomes 5/152,290 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,380
Admixed American	0.00667%	15,000
Remaining individualsnot grpmax-eligible	0.0048%	20,826

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.Arg641=
Coding: c.1921A>C
MANE Select: NM_198525
dbSNP: rs137905815
Type: single nucleotide variant
Location: chr15:89645894 (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 641: a UniProt-annotated variant site (in bbs; the patient also carries homozygous mutation r-390 in bbs1; may affect splicing; hypomorphic variant in vitro); the 'interaction with smo' region; the 'sufficient for interaction with nphp1' 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.Arg641Gly 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-arg641 (accessed [today's date]).

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