Is CTSF p.Ala481Val (c.1442C>T) pathogenic?

CTSF p.Ala481Val (c.1442C>T) is classified Uncertain significance in CTSF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-27). AlphaMissense: likely pathogenic (0.6283); Very rare (popmax 0.00666%, amr); Associated with Inborn genetic diseases.

What condition is associated with CTSF p.Ala481Val (c.1442C>T)?

CTSF p.Ala481Val (c.1442C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CTSF p.Ala481Val (c.1442C>T) in the general population?

CTSF p.Ala481Val (c.1442C>T) is very rare (popmax 0.00666%, amr) (gnomAD).

What do computational predictors say about CTSF p.Ala481Val (c.1442C>T)?

AlphaMissense predicts likely pathogenic (score 0.6283) — an in-silico prediction, not a clinical call.

CTSF p.Ala481Val

c.1442C>T · rs768809245 · VCV1772728

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6283 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6283	likely pathogenic
REVEL	0.394	indeterminate
SaProt	LLR -7.78	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 4,550 bp · p 0.69 · regional, not allelic
Overall
CADD	26.1	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 0.00666% Admixed American · 4/60,018 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00242% 39/1,612,978 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00666%	15,004
East Asian	0.00446%	22,438
Remaining individualsnot grpmax-eligible	0.0032%	31,205
European (non-Finnish)	0.00246%	40,690
South Asian	0.0022%	45,525

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.Ala481Val
Coding: c.1442C>T
MANE Select: NM_003793
dbSNP: rs768809245
Type: single nucleotide variant
Location: chr11:66563946 (GRCh38)
Gene constraint: LOEUF 1.296 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.78 · 1 PDB
Residue 481: a β-strand

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-ala481val (accessed [today's date]).

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