Is CTSK p.Val6Phe (c.16G>T) pathogenic?

CTSK p.Val6Phe (c.16G>T) is classified Conflicting classifications of pathogenicity in CTSK (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-03). AlphaMissense: likely benign (0.0663); Ultra-rare (popmax 0.0707%, afr); Associated with Inborn genetic diseases.

What condition is associated with CTSK p.Val6Phe (c.16G>T)?

CTSK p.Val6Phe (c.16G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CTSK p.Val6Phe (c.16G>T) in the general population?

CTSK p.Val6Phe (c.16G>T) is ultra-rare (popmax 0.0707%, afr) (gnomAD).

What do computational predictors say about CTSK p.Val6Phe (c.16G>T)?

AlphaMissense predicts likely benign (score 0.0663) — an in-silico prediction, not a clinical call.

CTSK p.Val6Phe

c.16G>T · rs201086925 · VCV1584563

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0663 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0707%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0663	likely benign
REVEL	0.432	indeterminate
SaProt	LLR -6.11	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.85	GERP -3.7
Regional constraint	o/e 0.73	unconstrained · MANE · 10 kb · p 6.6e-08 · regional, not allelic
Overall
CADD	9.483	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 0.0707% African / African-American · 53/75,000 alleles

Filtering AF 0.0554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0501%

Overall 0.00434% 70/1,613,986 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0707%	1,415
Middle Eastern	0.0165%	6,062
Admixed American	0.00167%	60,004
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)	0.0011%	90,770
South Asian	0.0011%	91,072

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: CTSK
Protein: p.Val6Phe
Coding: c.16G>T
MANE Select: NM_000396
dbSNP: rs201086925
Type: single nucleotide variant
Location: chr1:150806790 (GRCh38)
Gene constraint: LOEUF 0.748 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.89 · 70 PDB

Full CTSK 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

CTSK p.Val6= Likely benign ★ same residue
CTSK p.Asn301Tyr Uncertain significance ★★ ⚠ same condition
CTSK p.Asn53Ile Uncertain significance ★★ ⚠ same condition
CTSK p.Glu208Asp Uncertain significance ★★ ⚠ same condition
CTSK p.Leu22Met Uncertain significance ★★ ⚠ same condition
CTSK p.Ala240Thr Uncertain significance ★ ⚠ same condition
CTSK p.Ala311Pro Conflicting classifications of pathogenicity ★ ⚠ same condition
CTSK p.Ala317Thr 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/ctsk-p-val6phe (accessed [today's date]).

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