Is KIF7 p.Ser1122= (c.3366G>A) pathogenic?

KIF7 p.Ser1122= (c.3366G>A) is classified Conflicting classifications of pathogenicity in KIF7 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-04-16). Very rare (popmax 0.00223%, eas); Associated with acrocallosal syndrome.

What condition is associated with KIF7 p.Ser1122= (c.3366G>A)?

KIF7 p.Ser1122= (c.3366G>A) is associated with acrocallosal syndrome, multiple epiphyseal dysplasia, Al-Gazali type, hydrolethalus syndrome 2 (ClinVar).

How common is KIF7 p.Ser1122= (c.3366G>A) in the general population?

KIF7 p.Ser1122= (c.3366G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

KIF7 p.Ser1122=

c.3366G>A · rs771583869 · VCV2147972

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

acrocallosal syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.65	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -2	GERP -5.1
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,890 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000683% 11/1,610,584 alleles · very rare exomes 10/1,458,382 · genomes 1/152,202 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,890
African / African-American	0.00133%	74,934
European (non-Finnish)	0.000763%	131,111

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.Ser1122=
Coding: c.3366G>A
MANE Select: NM_198525
dbSNP: rs771583869
Type: single nucleotide variant
Location: chr15:89629526 (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 1122: the 'interaction with smo' region; a UniProt-annotated variant site (in acls; uncertain significance; atypical phenotype)

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.Ser1122Leu Uncertain significance ★★ ⚠ same residue
TICRR p.Arg1122Gly 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

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-ser1122 (accessed [today's date]).

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