Is KIF7 p.Val693Phe (c.2077G>T) pathogenic?

KIF7 p.Val693Phe (c.2077G>T) is classified Benign/Likely benign in KIF7 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-26). AlphaMissense: likely benign (0.0956); Rare (popmax 0.49%, sas); Associated with acrocallosal syndrome.

What condition is associated with KIF7 p.Val693Phe (c.2077G>T)?

KIF7 p.Val693Phe (c.2077G>T) is associated with acrocallosal syndrome (ClinVar).

How common is KIF7 p.Val693Phe (c.2077G>T) in the general population?

KIF7 p.Val693Phe (c.2077G>T) is rare (popmax 0.49%, sas) (gnomAD).

What do computational predictors say about KIF7 p.Val693Phe (c.2077G>T)?

AlphaMissense predicts likely benign (score 0.0956) — an in-silico prediction, not a clinical call.

KIF7 p.Val693Phe

c.2077G>T · rs550326630 · VCV317363

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0956 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.49%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

acrocallosal syndrome

Computational evidence

Protein change
AlphaMissense	0.0956	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -8.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.39	GERP 0.17, phastCons 0.069
Regional constraint	o/e 1.09	unconstrained · MANE · 25 kb · p 0.00011 · regional, not allelic
Overall
CADD	8.79	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 0.49% South Asian · 446/91,082 alleles

Filtering AF 0.452% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.437%

Overall 0.0288% 463/1,604,884 alleles · rare exomes 449/1,452,582 · genomes 14/152,302 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.49%	204
Remaining individualsnot grpmax-eligible	0.024%	4,162
Middle Eastern	0.0165%	6,060
European (non-Finnish)	8.47e-05%	1,179,962

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.Val693Phe
Coding: c.2077G>T
MANE Select: NM_198525
dbSNP: rs550326630
Type: single nucleotide variant
Location: chr15:89645127 (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 693: 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.Val693= 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
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-val693phe (accessed [today's date]).

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