Is CTSF p.Val286Leu (c.856G>C) pathogenic?

CTSF p.Val286Leu (c.856G>C) is classified Uncertain significance in CTSF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-20). AlphaMissense: likely pathogenic (0.7903); Very rare (popmax 0.00449%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CTSF p.Val286Leu (c.856G>C)?

CTSF p.Val286Leu (c.856G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CTSF p.Val286Leu (c.856G>C) in the general population?

CTSF p.Val286Leu (c.856G>C) is very rare (popmax 0.00449%, nfe) (gnomAD).

What do computational predictors say about CTSF p.Val286Leu (c.856G>C)?

AlphaMissense predicts likely pathogenic (score 0.7903) — an in-silico prediction, not a clinical call.

CTSF p.Val286Leu

c.856G>C · rs771943482 · VCV2224139

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7903 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00449%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7903	likely pathogenic
REVEL	0.889	moderately pathogenic-leaning
SaProt	LLR -13.14	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 2.6, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 4,550 bp · p 0.69 · regional, not allelic
Overall
CADD	26.2	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 0.00449% European (non-Finnish) · 53/1,180,024 alleles

Filtering AF 0.0035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.00335% 54/1,614,044 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00449%	22,265
African / African-American	0.00133%	74,932

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: CTSF
Protein: p.Val286Leu
Coding: c.856G>C
MANE Select: NM_003793
dbSNP: rs771943482
Type: single nucleotide variant
Location: chr11:66566033 (GRCh38)
Gene constraint: LOEUF 1.296 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.78 · 1 PDB
Residue 286: an α-helix

Full CTSF 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

CTSF c.1045+1G>T Likely pathogenic ★★ same condition
CTSF p.Arg217Ter Pathogenic ★★ same condition
CTSF p.Arg121Pro Uncertain significance ★★ ⚠ same condition
CTSF p.Arg196Trp Uncertain significance ★★ ⚠ same condition
CTSF p.Arg418Cys Uncertain significance ★★ ⚠ same condition
CTSF p.Arg421Gln Uncertain significance ★★ ⚠ same condition
CTSF p.Arg54Gly Uncertain significance ★★ ⚠ same condition
CTSF p.Asn213Lys 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/ctsf-p-val286leu (accessed [today's date]).

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