Is CTRL p.Cys201Tyr (c.602G>A) pathogenic?

CTRL p.Cys201Tyr (c.602G>A) is classified Uncertain significance in CTRL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely pathogenic (0.9944); Ultra-rare (popmax 0.0453%, afr).

How common is CTRL p.Cys201Tyr (c.602G>A) in the general population?

CTRL p.Cys201Tyr (c.602G>A) is ultra-rare (popmax 0.0453%, afr) (gnomAD).

What do computational predictors say about CTRL p.Cys201Tyr (c.602G>A)?

AlphaMissense predicts likely pathogenic (score 0.9944) — an in-silico prediction, not a clinical call.

CTRL p.Cys201Tyr

c.602G>A · rs201073485 · VCV2570460

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9944 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0453%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9944	likely pathogenic · top 1% in CTRL
REVEL	0.923	moderately pathogenic-leaning
SaProt	LLR -15.84	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.50 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6	phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 1,915 bp · p 0.39 · regional, not allelic
Overall
CADD	25.8	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 0.0453% African / African-American · 34/75,030 alleles

Filtering AF 0.0333% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0291%

Overall 0.0026% 42/1,614,040 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0453%	2,207
Admixed American	0.00333%	30,008
Remaining individualsnot grpmax-eligible	0.0032%	31,254
European (non-Finnish)	0.000339%	295,006

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: CTRL
Protein: p.Cys201Tyr
Coding: c.602G>A
MANE Select: NM_001907
dbSNP: rs201073485
Type: single nucleotide variant
Location: chr16:67930216 (GRCh38)
Gene constraint: LOEUF 1.372 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.26
Residue 201: a disulfide bond; the peptidase s1 domain

Full CTRL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTRL p.Gly230Ser Uncertain significance ★★ ⚠ same type
CTRL p.Glu151Gln Benign ★★ same type
CTRL p.Val70= Benign ★★ same type
CTRL p.Ala131Thr Uncertain significance ★ ⚠ same type
CTRL p.Ala27Thr Uncertain significance ★ ⚠ same type
CTRL p.Arg136His Uncertain significance ★ ⚠ same type
CTRL p.Arg162His Uncertain significance ★ ⚠ same type
CTRL p.Arg188Trp Uncertain significance ★ ⚠ same type

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/ctrl-p-cys201tyr (accessed [today's date]).

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